{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T06:13:21Z","timestamp":1794377601409,"version":"4.9.0"},"reference-count":283,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T00:00:00Z","timestamp":1752451200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T00:00:00Z","timestamp":1752451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Rev Drug Discov"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1038\/s41573-025-01236-y","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T16:06:36Z","timestamp":1752509196000},"page":"907-925","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["CRISPR-based therapeutic genome editing for inherited blood disorders\u00a0\u00a0"],"prefix":"10.1038","volume":"24","author":[{"given":"S\u00e9bastien","family":"Levesque","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5076-7945","authenticated-orcid":false,"given":"Daniel E.","family":"Bauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,14]]},"reference":[{"key":"1236_CR1","doi-asserted-by":"publisher","first-page":"1709","DOI":"10.1126\/science.1138140","volume":"315","author":"R Barrangou","year":"2007","unstructured":"Barrangou, R. et al. CRISPR provides acquired resistance against viruses in prokaryotes. Science 315, 1709\u20131712 (2007).","journal-title":"Science"},{"key":"1236_CR2","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/nature09523","volume":"468","author":"JE Garneau","year":"2010","unstructured":"Garneau, J. E. et al. The CRISPR\/Cas bacterial immune system cleaves bacteriophage and plasmid DNA. Nature 468, 67\u201371 (2010).","journal-title":"Nature"},{"key":"1236_CR3","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1126\/science.1225829","volume":"337","author":"M Jinek","year":"2012","unstructured":"Jinek, M. et al. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337, 816\u2013822 (2012).","journal-title":"Science"},{"key":"1236_CR4","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1038\/nrmicro2315","volume":"8","author":"SJ Labrie","year":"2010","unstructured":"Labrie, S. J., Samson, J. E. & Moineau, S. Bacteriophage resistance mechanisms. Nat. Rev. Microbiol. 8, 317\u2013327 (2010).","journal-title":"Nat. Rev. Microbiol."},{"key":"1236_CR5","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1126\/science.1231143","volume":"339","author":"L Cong","year":"2013","unstructured":"Cong, L. et al. Multiplex genome engineering using CRISPR\/Cas systems. Science 339, 819\u2013823 (2013).","journal-title":"Science"},{"key":"1236_CR6","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1126\/science.1232033","volume":"339","author":"P Mali","year":"2013","unstructured":"Mali, P. et al. RNA-guided human genome engineering via Cas9. Science 339, 823\u2013826 (2013).","journal-title":"Science"},{"key":"1236_CR7","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1038\/nature17946","volume":"533","author":"AC Komor","year":"2016","unstructured":"Komor, A. C., Kim, Y. B., Packer, M. S., Zuris, J. A. & Liu, D. R. Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature 533, 420\u2013424 (2016).","journal-title":"Nature"},{"key":"1236_CR8","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1038\/nature24644","volume":"551","author":"NM Gaudelli","year":"2017","unstructured":"Gaudelli, N. M. et al. Programmable base editing of A\u2022T to G\u2022C in genomic DNA without DNA cleavage. Nature 551, 464\u2013471 (2017).","journal-title":"Nature"},{"key":"1236_CR9","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1038\/s41586-019-1711-4","volume":"576","author":"AV Anzalone","year":"2019","unstructured":"Anzalone, A. V. et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature 576, 149\u2013157 (2019).","journal-title":"Nature"},{"key":"1236_CR10","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.gde.2015.08.001","volume":"33","author":"DE Bauer","year":"2015","unstructured":"Bauer, D. E. & Orkin, S. H. Hemoglobin switching\u2019s surprise: the versatile transcription factor BCL11A is a master repressor of fetal hemoglobin. Curr. Opin. Genet. Dev. 33, 62\u201370 (2015).","journal-title":"Curr. Opin. Genet. Dev."},{"key":"1236_CR11","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.1056\/NEJMra1510865","volume":"376","author":"FB Piel","year":"2017","unstructured":"Piel, F. B., Steinberg, M. H. & Reese, D. C. Sickle cell disease. N. Engl. J. Med. 376, 1561\u20131573 (2017).","journal-title":"N. Engl. J. Med."},{"key":"1236_CR12","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1056\/NEJMoa2031054","volume":"384","author":"H Frangoul","year":"2021","unstructured":"Frangoul, H. et al. CRISPR\u2013Cas9 gene editing for sickle cell disease and \u03b2-thalassemia. N. Engl. J. Med. 384, 252\u2013260 (2021).","journal-title":"N. Engl. J. Med."},{"key":"1236_CR13","doi-asserted-by":"publisher","first-page":"11869","DOI":"10.1073\/pnas.0804799105","volume":"105","author":"G Lettre","year":"2008","unstructured":"Lettre, G. et al. DNA polymorphisms at the BCL11A, HBS1L-MYB, and \u03b2-globin loci associate with fetal hemoglobin levels and pain crises in sickle cell disease. Proc. Natl Acad. Sci. USA 105, 11869\u201311874 (2008).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1236_CR14","doi-asserted-by":"publisher","first-page":"1839","DOI":"10.1126\/science.1165409","volume":"322","author":"VG Sankaran","year":"2008","unstructured":"Sankaran, V. G. et al. Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A. Science 322, 1839\u20131842 (2008).","journal-title":"Science"},{"key":"1236_CR15","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1126\/science.1211053","volume":"334","author":"J Xu","year":"2011","unstructured":"Xu, J. et al. Correction of sickle cell disease in adult mice by interference with fetal hemoglobin silencing. Science 334, 993\u2013996 (2011).","journal-title":"Science"},{"key":"1236_CR16","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1126\/science.1242088","volume":"342","author":"DE Bauer","year":"2013","unstructured":"Bauer, D. E. et al. An erythroid enhancer of BCL11A subject to genetic variation determines fetal hemoglobin level. Science 342, 253\u2013258 (2013).","journal-title":"Science"},{"key":"1236_CR17","doi-asserted-by":"publisher","first-page":"1620","DOI":"10.1073\/pnas.0711566105","volume":"105","author":"M Uda","year":"2008","unstructured":"Uda, M. et al. Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of \u03b2-thalassemia. Proc. Natl Acad. Sci. USA 105, 1620\u20131625 (2008).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1236_CR18","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1038\/s41591-019-0401-y","volume":"25","author":"Y Wu","year":"2019","unstructured":"Wu, Y. et al. Highly efficient therapeutic gene editing of human hematopoietic stem cells. Nat. Med. 25, 776\u2013783 (2019).","journal-title":"Nat. Med."},{"key":"1236_CR19","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1038\/s41591-020-0790-y","volume":"26","author":"J Zeng","year":"2020","unstructured":"Zeng, J. et al. Therapeutic base editing of human hematopoietic stem cells. Nat. Med. 26, 535\u2013541 (2020).","journal-title":"Nat. Med."},{"key":"1236_CR20","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1038\/nature15521","volume":"527","author":"MC Canver","year":"2015","unstructured":"Canver, M. C. et al. BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis. Nature 527, 192\u2013197 (2015).","journal-title":"Nature"},{"key":"1236_CR21","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34479-z","volume":"13","author":"SM Siegner","year":"2022","unstructured":"Siegner, S. M. et al. Adenine base editing efficiently restores the function of Fanconi anemia hematopoietic stem and progenitor cells. Nat. Commun. 13, 6900 (2022).","journal-title":"Nat. Commun."},{"key":"1236_CR22","doi-asserted-by":"publisher","first-page":"eadh8162","DOI":"10.1126\/scitranslmed.adh8162","volume":"16","author":"MC Castiello","year":"2024","unstructured":"Castiello, M. C. et al. Exonic knockout and knockin gene editing in hematopoietic stem and progenitor cells rescues RAG1 immunodeficiency. Sci. Transl. Med. 16, eadh8162 (2024).","journal-title":"Sci. Transl. Med."},{"key":"1236_CR23","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09614-y","volume":"10","author":"M Pavel-Dinu","year":"2019","unstructured":"Pavel-Dinu, M. et al. Gene correction for SCID-X1 in long-term hematopoietic stem cells. Nat. Commun. 10, 1634 (2019).","journal-title":"Nat. Commun."},{"key":"1236_CR24","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1016\/j.stem.2020.12.015","volume":"28","author":"S Rao","year":"2021","unstructured":"Rao, S. et al. Dissecting ELANE neutropenia pathogenicity by human HSC gene editing. Cell Stem Cell 28, 833\u2013845.e5 (2021).","journal-title":"Cell Stem Cell"},{"key":"1236_CR25","doi-asserted-by":"publisher","first-page":"1398","DOI":"10.1016\/j.cell.2023.02.027","volume":"186","author":"GE McAuley","year":"2023","unstructured":"McAuley, G. E. et al. Human T cell generation is restored in CD3\u03b4 severe combined immunodeficiency through adenine base editing. Cell 186, 1398\u20131416.e23 (2023).","journal-title":"Cell"},{"key":"1236_CR26","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11962-8","volume":"10","author":"N Gomez-Ospina","year":"2019","unstructured":"Gomez-Ospina, N. et al. Human genome-edited hematopoietic stem cells phenotypically correct mucopolysaccharidosis type I. Nat. Commun. 10, 4045 (2019).","journal-title":"Nat. Commun."},{"key":"1236_CR27","doi-asserted-by":"publisher","first-page":"1782","DOI":"10.1016\/j.ymthe.2017.04.027","volume":"25","author":"L Xu","year":"2017","unstructured":"Xu, L. et al. CRISPR\/Cas9-mediated CCR5 ablation in human hematopoietic stem\/progenitor cells confers HIV-1 resistance in vivo. Mol. Ther. 25, 1782\u20131789 (2017).","journal-title":"Mol. Ther."},{"key":"1236_CR28","doi-asserted-by":"publisher","first-page":"1240","DOI":"10.1056\/NEJMoa1817426","volume":"381","author":"L Xu","year":"2019","unstructured":"Xu, L. et al. CRISPR-edited stem cells in a patient with HIV and acute lymphocytic leukemia. N. Engl. J. Med. 381, 1240\u20131247 (2019).","journal-title":"N. Engl. J. Med."},{"key":"1236_CR29","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1038\/s41573-019-0020-9","volume":"18","author":"M Cavazzana","year":"2019","unstructured":"Cavazzana, M., Bushman, F. D., Miccio, A., Andr\u00e9-Schmutz, I. & Six, E. Gene therapy targeting haematopoietic stem cells for inherited diseases: progress and challenges. Nat. Rev. Drug. Discov. 18, 447\u2013462 (2019).","journal-title":"Nat. Rev. Drug. Discov."},{"key":"1236_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28762-2","volume":"13","author":"F Tucci","year":"2022","unstructured":"Tucci, F., Galimberti, S., Naldini, L., Valsecchi, M. G. & Aiuti, A. A systematic review and meta-analysis of gene therapy with hematopoietic stem and progenitor cells for monogenic disorders. Nat. Commun. 13, 1315 (2022).","journal-title":"Nat. Commun."},{"key":"1236_CR31","doi-asserted-by":"publisher","first-page":"1844","DOI":"10.1038\/s41587-023-02121-y","volume":"42","author":"L Mukhametzyanova","year":"2024","unstructured":"Mukhametzyanova, L. et al. Activation of recombinases at specific DNA loci by zinc-finger domain insertions. Nat. Biotechnol. 42, 1844\u20131854 (2024).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR32","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1038\/s41586-024-07552-4","volume":"630","author":"MG Durrant","year":"2024","unstructured":"Durrant, M. G. et al. Bridge RNAs direct modular and programmable recombination of target and donor DNA. Nature 630, 984\u2013993 (2024).","journal-title":"Nature"},{"key":"1236_CR33","doi-asserted-by":"publisher","first-page":"2503","DOI":"10.1016\/j.cell.2021.03.025","volume":"184","author":"JK Nu\u00f1ez","year":"2021","unstructured":"Nu\u00f1ez, J. K. et al. Genome-wide programmable transcriptional memory by CRISPR-based epigenome editing. Cell 184, 2503\u20132519 (2021).","journal-title":"Cell"},{"key":"1236_CR34","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1038\/s41586-024-07087-8","volume":"627","author":"MA Cappelluti","year":"2024","unstructured":"Cappelluti, M. A. et al. Durable and efficient gene silencing in vivo by hit-and-run epigenome editing. Nature 627, 416\u2013423 (2024).","journal-title":"Nature"},{"key":"1236_CR35","first-page":"8096","volume":"14","author":"P Rouet","year":"1994","unstructured":"Rouet, P., Smih, F. & Jasin, M. Introduction of double-strand breaks into the genome of mouse cells by expression of a rare-cutting endonuclease. Mol. Cell Biol. 14, 8096\u20138106 (1994).","journal-title":"Mol. Cell Biol."},{"key":"1236_CR36","doi-asserted-by":"publisher","first-page":"1156","DOI":"10.1073\/pnas.93.3.1156","volume":"93","author":"YG Kim","year":"1996","unstructured":"Kim, Y. G., Cha, J. & Chandrasegaran, S. Hybrid restriction enzymes: zinc finger fusions to Fok I cleavage domain. Proc. Natl Acad. Sci. USA 93, 1156\u20131160 (1996).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1236_CR37","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1126\/science.1078395","volume":"300","author":"MH Porteus","year":"2003","unstructured":"Porteus, M. H. & Baltimore, D. Chimeric nucleases stimulate gene targeting in human cells. Science 300, 763 (2003).","journal-title":"Science"},{"key":"1236_CR38","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1038\/nature03556","volume":"435","author":"FD Urnov","year":"2005","unstructured":"Urnov, F. D. et al. Highly efficient endogenous human gene correction using designed zinc-finger nucleases. Nature 435, 646\u2013651 (2005).","journal-title":"Nature"},{"key":"1236_CR39","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/nature13420","volume":"510","author":"P Genovese","year":"2014","unstructured":"Genovese, P. et al. Targeted genome editing in human repopulating haematopoietic stem cells. Nature 510, 235\u2013240 (2014).","journal-title":"Nature"},{"key":"1236_CR40","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1038\/nbt1410","volume":"26","author":"EE Perez","year":"2008","unstructured":"Perez, E. E. et al. Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases. Nat. Biotechnol. 26, 808\u2013816 (2008).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR41","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1056\/NEJMoa1300662","volume":"370","author":"P Tebas","year":"2014","unstructured":"Tebas, P. et al. Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV. N. Engl. J. Med. 370, 901\u2013910 (2014).","journal-title":"N. Engl. J. Med."},{"key":"1236_CR42","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1126\/science.1178811","volume":"326","author":"J Boch","year":"2009","unstructured":"Boch, J. et al. Breaking the code of DNA binding specificity of TAL-type III effectors. Science 326, 1509\u20131512 (2009).","journal-title":"Science"},{"key":"1236_CR43","doi-asserted-by":"publisher","first-page":"1501","DOI":"10.1126\/science.1178817","volume":"326","author":"MJ Moscou","year":"2009","unstructured":"Moscou, M. J. & Bogdanove, A. J. A simple cipher governs DNA recognition by TAL effectors. Science 326, 1501 (2009).","journal-title":"Science"},{"key":"1236_CR44","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/nbt.1755","volume":"29","author":"JC Miller","year":"2011","unstructured":"Miller, J. C. et al. A TALE nuclease architecture for efficient genome editing. Nat. Biotechnol. 29, 143\u2013150 (2011).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR45","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/s41579-019-0299-x","volume":"18","author":"KS Makarova","year":"2020","unstructured":"Makarova, K. S. et al. Evolutionary classification of CRISPR\u2013Cas systems: a burst of class 2 and derived variants. Nat. Rev. Microbiol. 18, 67\u201383 (2020).","journal-title":"Nat. Rev. Microbiol."},{"key":"1236_CR46","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1038\/nrmicro3569","volume":"13","author":"KS Makarova","year":"2015","unstructured":"Makarova, K. S. et al. An updated evolutionary classification of CRISPR\u2013Cas systems. Nat. Rev. Microbiol. 13, 722\u2013736 (2015).","journal-title":"Nat. Rev. Microbiol."},{"key":"1236_CR47","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.mib.2017.05.008","volume":"37","author":"EV Koonin","year":"2017","unstructured":"Koonin, E. V., Makarova, K. S. & Zhang, F. Diversity, classification and evolution of CRISPR\u2013Cas systems. Curr. Opin. Microbiol. 37, 67\u201378 (2017).","journal-title":"Curr. Opin. Microbiol."},{"key":"1236_CR48","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1038\/nature13579","volume":"513","author":"C Anders","year":"2014","unstructured":"Anders, C., Niewoehner, O., Duerst, A. & Jinek, M. Structural basis of PAM-dependent target DNA recognition by the Cas9 endonuclease. Nature 513, 569\u2013573 (2014).","journal-title":"Nature"},{"key":"1236_CR49","doi-asserted-by":"publisher","first-page":"5853","DOI":"10.1073\/pnas.1913445117","volume":"117","author":"IE Ivanov","year":"2020","unstructured":"Ivanov, I. E. et al. Cas9 interrogates DNA in discrete steps modulated by mismatches and supercoiling. Proc. Natl Acad. Sci. USA 117, 5853\u20135860 (2020).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1236_CR50","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1038\/s41594-019-0258-2","volume":"26","author":"X Zhu","year":"2019","unstructured":"Zhu, X. et al. Cryo-EM structures reveal coordinated domain motions that govern DNA cleavage by Cas9. Nat. Struct. Mol. Biol. 26, 679\u2013685 (2019).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"1236_CR51","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1038\/s41586-022-05114-0","volume":"609","author":"M Pacesa","year":"2022","unstructured":"Pacesa, M. et al. R-loop formation and conformational activation mechanisms of Cas9. Nature 609, 191\u2013196 (2022).","journal-title":"Nature"},{"key":"1236_CR52","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1016\/j.molcel.2021.12.026","volume":"82","author":"TS Nambiar","year":"2022","unstructured":"Nambiar, T. S., Baudrier, L., Billon, P. & Ciccia, A. CRISPR-based genome editing through the lens of DNA repair. Mol. Cell 82, 348\u2013388 (2022).","journal-title":"Mol. Cell"},{"key":"1236_CR53","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/ncb3452","volume":"19","author":"N Hustedt","year":"2017","unstructured":"Hustedt, N. & Durocher, D. The control of DNA repair by the cell cycle. Nat. Cell Biol. 19, 1\u20139 (2017).","journal-title":"Nat. Cell Biol."},{"key":"1236_CR54","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1016\/j.dnarep.2008.06.018","volume":"7","author":"Z Mao","year":"2008","unstructured":"Mao, Z., Bozzella, M., Seluanov, A. & Gorbunova, V. Comparison of nonhomologous end joining and homologous recombination in human cells. DNA Repair. 7, 1765\u20131771 (2008).","journal-title":"DNA Repair."},{"key":"1236_CR55","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.stem.2024.11.001","volume":"32","author":"J Zeng","year":"2025","unstructured":"Zeng, J. et al. Gene editing without ex vivo culture evades genotoxicity in human hematopoietic stem cells. Cell Stem Cell 32, 191\u2013208 (2025).","journal-title":"Cell Stem Cell"},{"key":"1236_CR56","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1038\/nature14299","volume":"520","author":"FA Ran","year":"2015","unstructured":"Ran, F. A. et al. In vivo genome editing using Staphylococcus aureus Cas9. Nature 520, 186\u2013191 (2015).","journal-title":"Nature"},{"key":"1236_CR57","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1016\/j.cell.2015.08.007","volume":"162","author":"H Nishimasu","year":"2015","unstructured":"Nishimasu, H. et al. Crystal structure of Staphylococcus aureus Cas9. Cell 162, 1113\u20131126 (2015).","journal-title":"Cell"},{"key":"1236_CR58","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1101\/gr.255414.119","volume":"30","author":"D Agudelo","year":"2020","unstructured":"Agudelo, D. et al. Versatile and robust genome editing with Streptococcus thermophilus CRISPR1\u2013Cas9. Genome Res. 30, 107\u2013117 (2020).","journal-title":"Genome Res."},{"key":"1236_CR59","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-018-1591-1","volume":"19","author":"N Amrani","year":"2018","unstructured":"Amrani, N. et al. NmeCas9 is an intrinsically high-fidelity genome editing platform. Genome Biol. 19, 214 (2018).","journal-title":"Genome Biol."},{"key":"1236_CR60","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1016\/j.cell.2015.09.038","volume":"163","author":"B Zetsche","year":"2015","unstructured":"Zetsche, B. et al. Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR\u2013Cas system. Cell 163, 759\u2013771 (2015).","journal-title":"Cell"},{"key":"1236_CR61","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1038\/s41591-018-0326-x","volume":"25","author":"CT Charlesworth","year":"2019","unstructured":"Charlesworth, C. T. et al. Identification of preexisting adaptive immunity to Cas9 proteins in humans. Nat. Med. 25, 249\u2013254 (2019).","journal-title":"Nat. Med."},{"key":"1236_CR62","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/nature14592","volume":"523","author":"BP Kleinstiver","year":"2015","unstructured":"Kleinstiver, B. P. et al. Engineered CRISPR\u2013Cas9 nucleases with altered PAM specificities. Nature 523, 481\u2013485 (2015).","journal-title":"Nature"},{"key":"1236_CR63","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/nature26155","volume":"556","author":"JH Hu","year":"2018","unstructured":"Hu, J. H. et al. Evolved Cas9 variants with broad PAM compatibility and high DNA specificity. Nature 556, 57\u201363 (2018).","journal-title":"Nature"},{"key":"1236_CR64","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1126\/science.aas9129","volume":"361","author":"H Nishimasu","year":"2018","unstructured":"Nishimasu, H. et al. Engineered CRISPR\u2013Cas9 nuclease with expanded targeting space. Science 361, 1259\u20131262 (2018).","journal-title":"Science"},{"key":"1236_CR65","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1038\/s41587-020-0412-8","volume":"38","author":"SM Miller","year":"2020","unstructured":"Miller, S. M. et al. Continuous evolution of SpCas9 variants compatible with non-G PAMs. Nat. Biotechnol. 38, 471\u2013481 (2020).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR66","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1126\/science.aba8853","volume":"368","author":"RT Walton","year":"2020","unstructured":"Walton, R. T., Christie, K. A., Whittaker, M. N. & Kleinstiver, B. P. Unconstrained genome targeting with near-PAMless engineered CRISPR\u2013Cas9 variants. Science 368, 290\u2013296 (2020).","journal-title":"Science"},{"key":"1236_CR67","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1016\/j.tips.2020.04.009","volume":"41","author":"S Levesque","year":"2020","unstructured":"Levesque, S., Agudelo, D. & Doyon, Y. Rewired Cas9s with minimal sequence constraints. Trends Pharmacol. Sci. 41, 429\u2013431 (2020).","journal-title":"Trends Pharmacol. Sci."},{"key":"1236_CR68","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1038\/nature16526","volume":"529","author":"BP Kleinstiver","year":"2016","unstructured":"Kleinstiver, B. P. et al. High-fidelity CRISPR\u2013Cas9 nucleases with no detectable genome-wide off-target effects. Nature 529, 490\u2013495 (2016).","journal-title":"Nature"},{"key":"1236_CR69","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1126\/science.aad5227","volume":"351","author":"IM Slaymaker","year":"2016","unstructured":"Slaymaker, I. M. et al. Rationally engineered Cas9 nucleases with improved specificity. Science 351, 84\u201388 (2016).","journal-title":"Science"},{"key":"1236_CR70","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05477-x","volume":"9","author":"JK Lee","year":"2018","unstructured":"Lee, J. K. et al. Directed evolution of CRISPR\u2013Cas9 to increase its specificity. Nat. Commun. 9, 3048 (2018).","journal-title":"Nat. Commun."},{"key":"1236_CR71","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1038\/s41591-018-0137-0","volume":"24","author":"CA Vakulskas","year":"2018","unstructured":"Vakulskas, C. A. et al. A high-fidelity Cas9 mutant delivered as a ribonucleoprotein complex enables efficient gene editing in human hematopoietic stem and progenitor cells. Nat. Med. 24, 1216\u20131224 (2018).","journal-title":"Nat. Med."},{"key":"1236_CR72","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1038\/nature20134","volume":"539","author":"DP Dever","year":"2016","unstructured":"Dever, D. P. et al. CRISPR\/Cas9 \u03b2-globin gene targeting in human haematopoietic stem cells. Nature 539, 384\u2013389 (2016).","journal-title":"Nature"},{"key":"1236_CR73","doi-asserted-by":"publisher","first-page":"360ra134","DOI":"10.1126\/scitranslmed.aaf9336","volume":"8","author":"MA DeWitt","year":"2016","unstructured":"DeWitt, M. A. et al. Selection-free genome editing of the sickle mutation in human adult hematopoietic stem\/progenitor cells. Sci. Transl. Med. 8, 360ra134 (2016).","journal-title":"Sci. Transl. Med."},{"key":"1236_CR74","doi-asserted-by":"publisher","first-page":"108093","DOI":"10.1016\/j.celrep.2020.108093","volume":"32","author":"JJ Shin","year":"2020","unstructured":"Shin, J. J. et al. Controlled cycling and quiescence enables efficient HDR in engraftment-enriched adult hematopoietic stem and progenitor cells. Cell Rep. 32, 108093 (2020).","journal-title":"Cell Rep."},{"key":"1236_CR75","doi-asserted-by":"publisher","first-page":"2597","DOI":"10.1182\/blood-2014-12-615948","volume":"125","author":"MD Hoban","year":"2015","unstructured":"Hoban, M. D. et al. Correction of the sickle cell disease mutation in human hematopoietic stem\/progenitor cells. Blood 125, 2597\u20132604 (2015).","journal-title":"Blood"},{"key":"1236_CR76","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1089\/hum.2023.29234.bfs","volume":"34","author":"A Philippidis","year":"2023","unstructured":"Philippidis, A. Graphite bio pauses lead gene editing program in sickle cell disease. Hum. Gene Ther. 34, 90 (2023).","journal-title":"Hum. Gene Ther."},{"key":"1236_CR77","doi-asserted-by":"publisher","first-page":"1428","DOI":"10.1016\/j.stem.2022.09.001","volume":"29","author":"S Ferrari","year":"2022","unstructured":"Ferrari, S. et al. Choice of template delivery mitigates the genotoxic risk and adverse impact of editing in human hematopoietic stem cells. Cell Stem Cell 29, 1428\u20131444.e9 (2022).","journal-title":"Cell Stem Cell"},{"key":"1236_CR78","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12449-2","volume":"10","author":"KS Hanlon","year":"2019","unstructured":"Hanlon, K. S. et al. High levels of AAV vector integration into CRISPR-induced DNA breaks. Nat. Commun. 10, 4439 (2019).","journal-title":"Nat. Commun."},{"key":"1236_CR79","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-024-02171-w","author":"FP Suchy","year":"2024","unstructured":"Suchy, F. P. et al. Genome engineering with Cas9 and AAV repair templates generates frequent concatemeric insertions of viral vectors. Nat. Biotechnol. https:\/\/doi.org\/10.1038\/s41587-024-02171-w (2024).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR80","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1038\/s41587-022-01418-8","volume":"41","author":"BR Shy","year":"2023","unstructured":"Shy, B. R. et al. High-yield genome engineering in primary cells using a hybrid ssDNA repair template and small-molecule cocktails. Nat. Biotechnol. 41, 521\u2013531 (2023).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR81","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-024-02504-9","author":"K Xie","year":"2024","unstructured":"Xie, K. et al. Efficient non-viral immune cell engineering using circular single-stranded DNA-mediated genomic integration. Nat. Biotechnol. https:\/\/doi.org\/10.1038\/s41587-024-02504-9 (2024).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR82","doi-asserted-by":"publisher","first-page":"1479","DOI":"10.1016\/j.cell.2013.12.001","volume":"155","author":"B Chen","year":"2013","unstructured":"Chen, B. et al. Dynamic imaging of genomic loci in living human cells by an optimized CRISPR\/Cas system. Cell 155, 1479\u20131491 (2013).","journal-title":"Cell"},{"key":"1236_CR83","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1016\/j.cell.2013.06.044","volume":"154","author":"LA Gilbert","year":"2013","unstructured":"Gilbert, L. A. et al. CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes. Cell 154, 442\u2013451 (2013).","journal-title":"Cell"},{"key":"1236_CR84","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1038\/nmeth.2600","volume":"10","author":"P Perez-pinera","year":"2013","unstructured":"Perez-pinera, P. et al. RNA-guided gene activation by CRISPR\u2013Cas9-based transcription factors. Nat. Methods 10, 973\u2013979 (2013).","journal-title":"Nat. Methods"},{"key":"1236_CR85","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1038\/nmeth.3312","volume":"12","author":"A Chavez","year":"2015","unstructured":"Chavez, A. et al. Highly efficient Cas9-mediated transcriptional programming. Nat. Methods 12, 326\u2013328 (2015).","journal-title":"Nat. Methods"},{"key":"1236_CR86","doi-asserted-by":"publisher","first-page":"aaf8729","DOI":"10.1126\/science.aaf8729","volume":"353","author":"K Nishida","year":"2016","unstructured":"Nishida, K. et al. Targeted nucleotide editing using hybrid prokaryotic and vertebrate adaptive immune systems. Science 353, aaf8729 (2016).","journal-title":"Science"},{"key":"1236_CR87","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1126\/science.aad8282","volume":"351","author":"F Jiang","year":"2016","unstructured":"Jiang, F. et al. Structures of a CRISPR\u2013Cas9 R-loop complex primed for DNA cleavage. Science 351, 867\u2013871 (2016).","journal-title":"Science"},{"key":"1236_CR88","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1038\/s41587-020-0561-9","volume":"38","author":"AV Anzalone","year":"2020","unstructured":"Anzalone, A. V., Koblan, L. W. & Liu, D. R. Genome editing with CRISPR\u2013Cas nucleases, base editors, transposases and prime editors. Nat. Biotechnol. 38, 824\u2013844 (2020).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR89","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1126\/science.aav9973","volume":"364","author":"E Zuo","year":"2019","unstructured":"Zuo, E. et al. Cytosine base editor generates substantial off-target single-nucleotide variants in mouse embryos. Science 364, 289\u2013292 (2019).","journal-title":"Science"},{"key":"1236_CR90","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1126\/science.aaw7166","volume":"364","author":"S Jin","year":"2019","unstructured":"Jin, S. et al. Cytosine, but not adenine, base editors induce genome-wide off-target mutations in rice. Science 364, 292\u2013295 (2019).","journal-title":"Science"},{"key":"1236_CR91","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1038\/s41587-020-0414-6","volume":"38","author":"JL Doman","year":"2020","unstructured":"Doman, J. L., Raguram, A., Newby, G. A. & Liu, D. R. Evaluation and minimization of Cas9-independent off-target DNA editing by cytosine base editors. Nat. Biotechnol. 38, 620\u2013628 (2020).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR92","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1038\/s41586-019-1161-z","volume":"569","author":"J Gr\u00fcnewald","year":"2019","unstructured":"Gr\u00fcnewald, J. et al. Transcriptome-wide off-target RNA editing induced by CRISPR-guided DNA base editors. Nature 569, 433\u2013437 (2019).","journal-title":"Nature"},{"key":"1236_CR93","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1038\/s41587-019-0236-6","volume":"37","author":"J Gr\u00fcnewald","year":"2019","unstructured":"Gr\u00fcnewald, J. et al. CRISPR DNA base editors with reduced RNA off-target and self-editing activities. Nat. Biotechnol. 37, 1041\u20131048 (2019).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR94","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1038\/s41587-023-01915-4","volume":"42","author":"M Fiumara","year":"2024","unstructured":"Fiumara, M. et al. Genotoxic effects of base and prime editing in human hematopoietic stem cells. Nat. Biotechnol. 42, 877\u2013891 (2024).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR95","doi-asserted-by":"publisher","first-page":"eaao4774","DOI":"10.1126\/sciadv.aao4774","volume":"3","author":"AC Komor","year":"2017","unstructured":"Komor, A. C. et al. Improved base excision repair inhibition and bacteriophage Mu Gam protein yields C:G-to-T:A base editors with higher efficiency and product purity. Sci. Adv. 3, eaao4774 (2017).","journal-title":"Sci. Adv."},{"key":"1236_CR96","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1038\/nbt.4172","volume":"36","author":"LW Koblan","year":"2018","unstructured":"Koblan, L. W. et al. Improving cytidine and adenine base editors by expression optimization and ancestral reconstruction. Nat. Biotechnol. 36, 843\u2013848 (2018).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR97","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1038\/s41587-020-0453-z","volume":"38","author":"MF Richter","year":"2020","unstructured":"Richter, M. F. et al. Phage-assisted evolution of an adenine base editor with improved Cas domain compatibility and activity. Nat. Biotechnol. 38, 883\u2013891 (2020).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR98","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1038\/s41587-020-0491-6","volume":"38","author":"NM Gaudelli","year":"2020","unstructured":"Gaudelli, N. M. et al. Directed evolution of adenine base editors with increased activity and therapeutic application. Nat. Biotechnol. 38, 892\u2013900 (2020).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR99","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1038\/s41587-022-01533-6","volume":"41","author":"ME Neugebauer","year":"2022","unstructured":"Neugebauer, M. E. et al. Evolution of an adenine base editor into a small, efficient cytosine base editor with low off-target activity. Nat. Biotechnol. 41, 673\u2013685 (2022).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR100","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1038\/s41587-022-01532-7","volume":"41","author":"L Chen","year":"2023","unstructured":"Chen, L. et al. Re-engineering the adenine deaminase TadA-8e for efficient and specific CRISPR-based cytosine base editing. Nat. Biotechnol. 41, 663\u2013672 (2023).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR101","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1038\/s41587-022-01611-9","volume":"41","author":"DK Lam","year":"2023","unstructured":"Lam, D. K. et al. Improved cytosine base editors generated from TadA variants. Nat. Biotechnol. 41, 686\u2013697 (2023).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR102","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1038\/s41586-021-03609-w","volume":"595","author":"GA Newby","year":"2021","unstructured":"Newby, G. A. et al. Base editing of haematopoietic stem cells rescues sickle cell disease in mice. Nature 595, 295\u2013302 (2021).","journal-title":"Nature"},{"key":"1236_CR103","doi-asserted-by":"publisher","first-page":"1210","DOI":"10.1038\/s41588-023-01434-7","volume":"55","author":"T Mayuranathan","year":"2023","unstructured":"Mayuranathan, T. et al. Potent and uniform fetal hemoglobin induction via base editing. Nat. Genet. 55, 1210\u20131220 (2023).","journal-title":"Nat. Genet."},{"key":"1236_CR104","doi-asserted-by":"publisher","first-page":"eadj6779","DOI":"10.1126\/scitranslmed.adj6779","volume":"16","author":"V Bzhilyanskaya","year":"2024","unstructured":"Bzhilyanskaya, V. et al. High-fidelity PAMless base editing of hematopoietic stem cells to treat chronic granulomatous disease. Sci. Transl. Med. 16, eadj6779 (2024).","journal-title":"Sci. Transl. Med."},{"key":"1236_CR105","doi-asserted-by":"publisher","first-page":"3882","DOI":"10.1128\/MCB.15.7.3882","volume":"15","author":"DD Luan","year":"1995","unstructured":"Luan, D. D. & Eickbush, T. H. RNA template requirements for target DNA-primed reverse transcription by the R2 retrotransposable element. Mol. Cell Biol. 15, 3882\u20133891 (1995).","journal-title":"Mol. Cell Biol."},{"key":"1236_CR106","doi-asserted-by":"publisher","first-page":"5635","DOI":"10.1016\/j.cell.2021.09.018","volume":"184","author":"PJ Chen","year":"2021","unstructured":"Chen, P. J. et al. Enhanced prime editing systems by manipulating cellular determinants of editing outcomes. Cell 184, 5635\u20135652 (2021).","journal-title":"Cell"},{"key":"1236_CR107","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28442-1","volume":"13","author":"J Ferreira da Silva","year":"2022","unstructured":"Ferreira da Silva, J. et al. Prime editing efficiency and fidelity are enhanced in the absence of mismatch repair. Nat. Commun. 13, 760 (2022).","journal-title":"Nat. Commun."},{"key":"1236_CR108","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33669-z","volume":"13","author":"S Levesque","year":"2022","unstructured":"Levesque, S. et al. Marker-free co-selection for successive rounds of prime editing in human cells. Nat. Commun. 13, 5909 (2022).","journal-title":"Nat. Commun."},{"key":"1236_CR109","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31322-3","volume":"13","author":"J Tao","year":"2022","unstructured":"Tao, J., Wang, Q., Mendez-Dorantes, C., Burns, K. H. & Chiarle, R. Frequency and mechanisms of LINE-1 retrotransposon insertions at CRISPR\/Cas9 sites. Nat. Commun. 13, 3685 (2022).","journal-title":"Nat. Commun."},{"key":"1236_CR110","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1016\/j.molcel.2007.04.018","volume":"26","author":"JJ Warren","year":"2007","unstructured":"Warren, J. J. et al. Structure of the human MutS\u03b1 DNA lesion recognition complex. Mol. Cell 26, 579\u2013592 (2007).","journal-title":"Mol. Cell"},{"key":"1236_CR111","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1038\/nsmb.2175","volume":"19","author":"S Gupta","year":"2012","unstructured":"Gupta, S., Gellert, M. & Yang, W. Mechanism of mismatch recognition revealed by human MutS\u03b2 bound to unpaired DNA loops. Nat. Struct. Mol. Biol. 19, 72\u201379 (2012).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"1236_CR112","doi-asserted-by":"publisher","first-page":"16066","DOI":"10.1073\/pnas.1010662107","volume":"107","author":"A Pluciennik","year":"2010","unstructured":"Pluciennik, A. et al. PCNA function in the activation and strand direction of MutL\u03b1 endonuclease in mismatch repair. Proc. Natl Acad. Sci. USA 107, 16066\u201316071 (2010).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1236_CR113","doi-asserted-by":"publisher","first-page":"13302","DOI":"10.1074\/jbc.M111854200","volume":"277","author":"J Genschel","year":"2002","unstructured":"Genschel, J., Bazemore, L. R. & Modrich, P. Human exonuclease I is required for 5\u2032 and 3\u2032 mismatch repair. J. Biol. Chem. 277, 13302\u201313311 (2002).","journal-title":"J. Biol. Chem."},{"key":"1236_CR114","doi-asserted-by":"publisher","first-page":"10917","DOI":"10.1074\/jbc.272.16.10917","volume":"272","author":"MJ Longley","year":"1997","unstructured":"Longley, M. J., Pierce, A. J. & Modrich, P. DNA polymerase \u03b4 is required for human mismatch repair in vitro. J. Biol. Chem. 272, 10917\u201310921 (1997).","journal-title":"J. Biol. Chem."},{"key":"1236_CR115","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/j.cell.2005.06.027","volume":"122","author":"Y Zhang","year":"2005","unstructured":"Zhang, Y. et al. Reconstitution of 5\u2032-directed human mismatch repair in a purified system. Cell 122, 693\u2013705 (2005).","journal-title":"Cell"},{"key":"1236_CR116","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1038\/s41551-023-01026-0","volume":"7","author":"KA Everette","year":"2023","unstructured":"Everette, K. A. et al. Ex vivo prime editing of patient haematopoietic stem cells rescues sickle-cell disease phenotypes after engraftment in mice. Nat. Biomed. Eng. 7, 616\u2013628 (2023).","journal-title":"Nat. Biomed. Eng."},{"key":"1236_CR117","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1038\/s41587-024-02266-4","volume":"43","author":"S Levesque","year":"2025","unstructured":"Levesque, S., Cosentino, A., Verma, A., Genovese, P. & Bauer, D. E. Enhancing prime editing in hematopoietic stem and progenitor cells by modulating nucleotide metabolism. Nat. Biotechnol. 43, 534\u2013538 (2025).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR118","doi-asserted-by":"publisher","first-page":"1822","DOI":"10.1038\/s41587-023-02106-x","volume":"42","author":"RP Kim-yip","year":"2023","unstructured":"Kim-yip, R. P. et al. Efficient prime editing in two-cell mouse embryos using PEmbryo. Nat. Biotechnol. 42, 1822\u20131830 (2023).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR119","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29339-9","volume":"13","author":"X Li","year":"2022","unstructured":"Li, X. et al. Highly efficient prime editing by introducing same-sense mutations in pegRNA or stabilizing its structure. Nat. Commun. 13, 1669 (2022).","journal-title":"Nat. Commun."},{"key":"1236_CR120","doi-asserted-by":"publisher","first-page":"6829","DOI":"10.1016\/S0021-9258(18)68718-6","volume":"263","author":"SS Su","year":"1988","unstructured":"Su, S. S., Lahue, R. S., Au, K. G. & Modrich, P. Mispair specificity of methyl-directed DNA mismatch correction in vitro. J. Biol. Chem. 263, 6829\u20136835 (1988).","journal-title":"J. Biol. Chem."},{"key":"1236_CR121","doi-asserted-by":"publisher","first-page":"3744","DOI":"10.1016\/S0021-9258(19)67858-0","volume":"266","author":"DC Thomas","year":"1991","unstructured":"Thomas, D. C., Roberts, J. D. & Kunkel, T. A. Heteroduplex repair in extracts of human HeLa cells. J. Biol. Chem. 266, 3744\u20133751 (1991).","journal-title":"J. Biol. Chem."},{"key":"1236_CR122","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1126\/science.2665076","volume":"245","author":"R Lahue","year":"1998","unstructured":"Lahue, R., Au, K. & Modrich, P. DNA mismatch correction in a defined system. Science 245, 160\u2013164 (1998).","journal-title":"Science"},{"key":"1236_CR123","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1038\/s41586-024-07259-6","volume":"628","author":"J Yan","year":"2024","unstructured":"Yan, J. et al. Improving prime editing with an endogenous small RNA-binding protein. Nature 628, 639\u2013647 (2024).","journal-title":"Nature"},{"key":"1236_CR124","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1038\/s41587-021-01039-7","volume":"40","author":"JW Nelson","year":"2021","unstructured":"Nelson, J. W. et al. Engineered pegRNAs improve prime editing efficiency. Nat. Biotechnol. 40, 402\u2013410 (2021).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR125","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1038\/s41587-021-01133-w","volume":"40","author":"AV Anzalone","year":"2022","unstructured":"Anzalone, A. V. et al. Programmable deletion, replacement, integration and inversion of large DNA sequences with twin prime editing. Nat. Biotechnol. 40, 731\u2013740 (2022).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR126","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1038\/s41592-022-01399-1","volume":"19","author":"J Wang","year":"2022","unstructured":"Wang, J. et al. Efficient targeted insertion of large DNA fragments without DNA donors. Nat. Methods 19, 331\u2013340 (2022).","journal-title":"Nat. Methods"},{"key":"1236_CR127","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1038\/s41587-021-01026-y","volume":"40","author":"T Jiang","year":"2021","unstructured":"Jiang, T., Zhang, X., Weng, Z. & Xue, W. Deletion and replacement of long genomic sequences using prime editing. Nat. Biotechnol. 40, 227\u2013234 (2021).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR128","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1038\/s41576-022-00541-1","volume":"24","author":"PJ Chen","year":"2022","unstructured":"Chen, P. J. & Liu, D. R. Prime editing for precise and highly versatile genome manipulation. Nat. Rev. Genet. 24, 161\u2013177 (2022).","journal-title":"Nat. Rev. Genet."},{"key":"1236_CR129","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1038\/s41587-021-01025-z","volume":"40","author":"J Choi","year":"2022","unstructured":"Choi, J. et al. Precise genomic deletions using paired prime editing. Nat. Biotechnol. 40, 218\u2013226 (2022).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR130","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1038\/s41551-024-01227-1","volume":"9","author":"S Pandey","year":"2025","unstructured":"Pandey, S. et al. Efficient site-specific integration of large genes in mammalian cells via continuously evolved recombinases and prime editing. Nat. Biomed. Eng. 9, 22\u201339 (2025).","journal-title":"Nat. Biomed. Eng."},{"key":"1236_CR131","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1038\/s41587-022-01527-4","volume":"41","author":"MTN Yarnall","year":"2022","unstructured":"Yarnall, M. T. N. et al. Drag-and-drop genome insertion of large sequences without double-strand DNA cleavage using CRISPR-directed integrases. Nat. Biotechnol. 41, 500\u2013512 (2022).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR132","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae534","volume":"52","author":"BE Hew","year":"2024","unstructured":"Hew, B. E. et al. Directed evolution of hyperactive integrases for site specific insertion of transgenes. Nucleic Acids Res. 52, e64 (2024).","journal-title":"Nucleic Acids Res."},{"key":"1236_CR133","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1038\/s41587-023-01748-1","volume":"42","author":"GD Lampe","year":"2024","unstructured":"Lampe, G. D. et al. Targeted DNA integration in human cells without double-strand breaks using CRISPR-associated transposases. Nat. Biotechnol. 42, 87\u201398 (2024).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR134","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1038\/s41577-022-00698-0","volume":"22","author":"CT Charlesworth","year":"2022","unstructured":"Charlesworth, C. T., Hsu, I., Wilkinson, A. C. & Nakauchi, H. Immunological barriers to haematopoietic stem cell gene therapy. Nat. Rev. Immunol. 22, 719\u2013733 (2022).","journal-title":"Nat. Rev. Immunol."},{"key":"1236_CR135","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1038\/s41577-021-00524-z","volume":"21","author":"A Decout","year":"2021","unstructured":"Decout, A., Katz, J. D., Venkatraman, S. & Ablasser, A. The cGAS\u2013STING pathway as a therapeutic target in inflammatory diseases. Nat. Rev. Immunol. 21, 548\u2013569 (2021).","journal-title":"Nat. Rev. Immunol."},{"key":"1236_CR136","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1126\/science.110.2865.543","volume":"110","author":"L Pauling","year":"1949","unstructured":"Pauling, L., Itano, H. A., Singer, S. & Wells, I. C. Sickle cell anemia, a molecular disease. Science 110, 543\u2013548 (1949).","journal-title":"Science"},{"key":"1236_CR137","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1038\/180326a0","volume":"180","author":"VM Ingram","year":"1957","unstructured":"Ingram, V. M. Gene mutations in human haemoglobin: the chemical difference between normal and sickle cell haemoglobin. Nature 180, 326\u2013328 (1957).","journal-title":"Nature"},{"key":"1236_CR138","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1056\/NEJMra2021838","volume":"384","author":"AT Taher","year":"2021","unstructured":"Taher, A. T., Musallam, K. M. & Cappellini, D. M. \u03b2-Thalassemias. N. Engl. J. Med. 384, 727\u2013743 (2021).","journal-title":"N. Engl. J. Med."},{"key":"1236_CR139","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1016\/j.bbmt.2016.03.003","volume":"22","author":"I Zaidman","year":"2016","unstructured":"Zaidman, I., Rowe, J. M., Khalil, A., Ben-Arush, M. & Elhasid, R. Allogeneic stem cell transplantation in congenital hemoglobinopathies using a tailored busulfan-based conditioning regimen: single-center experience. Biol. Blood Marrow Transplant. 22, 1043\u20131048 (2016).","journal-title":"Biol. Blood Marrow Transplant."},{"key":"1236_CR140","doi-asserted-by":"publisher","first-page":"214","DOI":"10.3324\/haematol.2015.141200","volume":"102","author":"A Srivastava","year":"2017","unstructured":"Srivastava, A. & Shaji, R. V. Cure for thalassemia major\u2014from allogeneic hematopoietic stem cell transplantation to gene therapy. Haematologica 102, 214\u2013223 (2017).","journal-title":"Haematologica"},{"key":"1236_CR141","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1080\/17474086.2023.2268271","volume":"16","author":"Z Inam","year":"2023","unstructured":"Inam, Z., Tisdale, J. F. & Leonard, A. Outcomes and long-term effects of hematopoietic stem cell transplant in sickle cell disease. Expert. Rev. Hematol. 16, 879\u2013903 (2023).","journal-title":"Expert. Rev. Hematol."},{"key":"1236_CR142","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1182\/blood-2022-162288","volume":"140","author":"MC Walters","year":"2022","unstructured":"Walters, M. C. et al. Lovo-cel (bb1111) gene therapy for sickle cell disease: updated clinical results and investigations into two cases of anemia from group C of the phase 1\/2 HGB-206 study. Blood 140, 26\u201328 (2022).","journal-title":"Blood"},{"key":"1236_CR143","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1111\/j.1749-6632.1998.tb10460.x","volume":"850","author":"BG Forget","year":"1998","unstructured":"Forget, B. G. Molecular basis of hereditary persistence of fetal hemoglobin. Ann. N. Y. Acad. Sci. 850, 38\u201344 (1998).","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"1236_CR144","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1038\/ng2108","volume":"39","author":"S Menzel","year":"2007","unstructured":"Menzel, S. et al. A QTL influencing F cell production maps to a gene encoding a zinc-finger protein on chromosome 2p15. Nat. Genet. 39, 1197\u20131199 (2007).","journal-title":"Nat. Genet."},{"key":"1236_CR145","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1038\/nm.4170","volume":"22","author":"EA Traxler","year":"2016","unstructured":"Traxler, E. A. et al. A genome-editing strategy to treat \u03b2-hemoglobinopathies that recapitulates a mutation associated with a benign genetic condition. Nat. Med. 22, 987\u2013990 (2016).","journal-title":"Nat. Med."},{"key":"1236_CR146","doi-asserted-by":"publisher","first-page":"1663","DOI":"10.1056\/NEJMoa2309673","volume":"390","author":"F Locatelli","year":"2024","unstructured":"Locatelli, F. et al. Exagamglogene autotemcel for transfusion-dependent \u03b2-thalassemia. N. Engl. J. Med. 390, 1663\u20131676 (2024).","journal-title":"N. Engl. J. Med."},{"key":"1236_CR147","doi-asserted-by":"publisher","first-page":"1649","DOI":"10.1056\/NEJMoa2309676","volume":"390","author":"H Frangoul","year":"2024","unstructured":"Frangoul, H. et al. Exagamglogene autotemcel for severe sickle cell disease. N. Engl. J. Med. 390, 1649\u20131662 (2024).","journal-title":"N. Engl. J. Med."},{"key":"1236_CR148","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.1038\/s41591-022-01906-z","volume":"28","author":"B Fu","year":"2022","unstructured":"Fu, B. et al. CRISPR\u2013Cas9-mediated gene editing of the BCL11A enhancer for pediatric \u03b20\/\u03b20 transfusion-dependent \u03b2-thalassemia. Nat. Med. 28, 1573\u20131580 (2022).","journal-title":"Nat. Med."},{"key":"1236_CR149","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1016\/j.tig.2018.09.004","volume":"34","author":"B Wienert","year":"2018","unstructured":"Wienert, B., Martyn, G. E., Funnell, A. P. W., Quinlan, K. G. R. & Crossley, M. Wake-up sleepy gene: reactivating fetal globin for \u03b2-hemoglobinopathies. Trends Genet. 34, 927\u2013940 (2018).","journal-title":"Trends Genet."},{"key":"1236_CR150","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.65421","volume":"11","author":"NS Ravi","year":"2022","unstructured":"Ravi, N. S. et al. Identification of novel HPFH-like mutations by CRISPR base editing that elevate the expression of fetal hemoglobin. eLife 11, e65421 (2022).","journal-title":"eLife"},{"key":"1236_CR151","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34493-1","volume":"13","author":"P Antoniou","year":"2022","unstructured":"Antoniou, P. et al. Base-editing-mediated dissection of a \u03b3-globin cis-regulatory element for the therapeutic reactivation of fetal hemoglobin expression. Nat. Commun. 13, 6618 (2022).","journal-title":"Nat. Commun."},{"key":"1236_CR152","doi-asserted-by":"publisher","first-page":"eabf2444","DOI":"10.1126\/scitranslmed.abf2444","volume":"13","author":"A Lattanzi","year":"2021","unstructured":"Lattanzi, A. et al. Development of \u03b2-globin gene correction in human hematopoietic stem cells as a potential durable treatment for sickle cell disease. Sci. Transl. Med 13, eabf2444 (2021).","journal-title":"Sci. Transl. Med"},{"key":"1236_CR153","first-page":"2085","volume":"141","author":"C Li","year":"2023","unstructured":"Li, C. et al. In vivo HSC prime editing rescues sickle cell disease in a mouse model. Blood 141, 2085\u20132099 (2023).","journal-title":"Blood"},{"key":"1236_CR154","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1089\/crispr.2020.0144","volume":"4","author":"SH Chu","year":"2021","unstructured":"Chu, S. H. et al. Rationally designed base editors for precise editing of the sickle cell disease mutation. CRISPR J. 4, 169\u2013177 (2021).","journal-title":"CRISPR J."},{"key":"1236_CR155","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.1093\/cid\/ciu1154","volume":"60","author":"BE Marciano","year":"2015","unstructured":"Marciano, B. E. et al. Common severe infections in chronic granulomatous disease. Clin. Infect. Dis. 60, 1176\u20131183 (2015).","journal-title":"Clin. Infect. Dis."},{"key":"1236_CR156","doi-asserted-by":"publisher","first-page":"eaah3480","DOI":"10.1126\/scitranslmed.aah3480","volume":"9","author":"SS De Ravin","year":"2017","unstructured":"De Ravin, S. S. et al. CRISPR\u2013Cas9 gene repair of hematopoietic stem cells from patients with X-linked chronic granulomatous disease. Sci. Transl. Med. 9, eaah3480 (2017).","journal-title":"Sci. Transl. Med."},{"key":"1236_CR157","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1016\/j.omtm.2020.04.015","volume":"17","author":"D Wrona","year":"2020","unstructured":"Wrona, D. et al. CRISPR-directed therapeutic correction at the NCF1 locus is challenged by frequent incidence of chromosomal deletions. Mol. Ther. Methods Clin. Dev. 17, 936\u2013943 (2020).","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"1236_CR158","doi-asserted-by":"publisher","first-page":"1291","DOI":"10.1038\/s42003-024-06959-z","volume":"7","author":"F Raimondi","year":"2024","unstructured":"Raimondi, F. et al. Gene editing of NCF1 loci is associated with homologous recombination and chromosomal rearrangements. Commun. Biol. 7, 1291 (2024).","journal-title":"Commun. Biol."},{"key":"1236_CR159","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1182\/blood-2005-11-4689","volume":"108","author":"I K\u00f6llner","year":"2006","unstructured":"K\u00f6llner, I. et al. Mutations in neutrophil elastase causing congenital neutropenia lead to cytoplasmic protein accumulation and induction of the unfolded protein response. Blood 108, 493\u2013500 (2006).","journal-title":"Blood"},{"key":"1236_CR160","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1097\/MOH.0b013e32834da96e","volume":"19","author":"JA Connelly","year":"2012","unstructured":"Connelly, J. A., Choi, S. W. & Levine, J. E. Hematopoietic stem cell transplantation for severe congenital neutropenia. Curr. Opin. Hematol. 19, 44\u201351 (2012).","journal-title":"Curr. Opin. Hematol."},{"key":"1236_CR161","doi-asserted-by":"publisher","first-page":"3103","DOI":"10.1172\/JCI80924","volume":"125","author":"RC Nayak","year":"2015","unstructured":"Nayak, R. C. et al. Pathogenesis of ELANE-mutant severe neutropenia revealed by induced pluripotent stem cells. J. Clin. Investig. 125, 3103\u20133116 (2015).","journal-title":"J. Clin. Investig."},{"key":"1236_CR162","doi-asserted-by":"publisher","first-page":"1817","DOI":"10.1182\/blood-2006-08-019166","volume":"109","author":"MS Horwitz","year":"2007","unstructured":"Horwitz, M. S. et al. Neutrophil elastase in cyclic and severe congenital neutropenia. Blood 109, 1817\u20131824 (2007).","journal-title":"Blood"},{"key":"1236_CR163","doi-asserted-by":"publisher","first-page":"4179","DOI":"10.1182\/blood-2006-11-057299","volume":"110","author":"DS Grenda","year":"2007","unstructured":"Grenda, D. S. et al. Mutations of the ELA2 gene found in patients with severe congenital neutropenia induce the unfolded protein response and cellular apoptosis. Blood 110, 4179\u20134187 (2007).","journal-title":"Blood"},{"key":"1236_CR164","doi-asserted-by":"publisher","first-page":"598","DOI":"10.3324\/haematol.2019.221804","volume":"105","author":"M Nasri","year":"2020","unstructured":"Nasri, M. et al. CRISPR\/Cas9-mediated ELANE knockout enables neutrophilic maturation of primary hematopoietic stem and progenitor cells and induced pluripotent stem cells of severe congenital neutropenia patients. Haematologica 105, 598\u2013609 (2020).","journal-title":"Haematologica"},{"key":"1236_CR165","doi-asserted-by":"publisher","first-page":"1628","DOI":"10.1016\/j.ymthe.2024.03.037","volume":"32","author":"M Nasri","year":"2024","unstructured":"Nasri, M. et al. CRISPR\u2013Cas9n-mediated ELANE promoter editing for gene therapy of severe congenital neutropenia. Mol. Ther. 32, 1628\u20131642 (2024).","journal-title":"Mol. Ther."},{"key":"1236_CR166","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.bbmt.2007.10.017","volume":"14","author":"MJ Cowan","year":"2008","unstructured":"Cowan, M. J., Neven, B., Cavazanna-Calvo, M., Fischer, A. & Puck, J. Hematopoietic stem cell transplantation for severe combined immunodeficiency diseases. Biol. Blood Marrow Transplant. 14, 73\u201380 (2008).","journal-title":"Biol. Blood Marrow Transplant."},{"key":"1236_CR167","doi-asserted-by":"publisher","first-page":"4114","DOI":"10.1182\/blood-2008-09-177923","volume":"113","author":"B Neven","year":"2009","unstructured":"Neven, B. et al. Long-term outcome after hematopoietic stem cell transplantation of a single-center cohort of 90 patients with severe combined immunodeficiency. Blood 113, 4114\u20134124 (2009).","journal-title":"Blood"},{"key":"1236_CR168","doi-asserted-by":"publisher","first-page":"1525","DOI":"10.1056\/NEJMoa1815408","volume":"380","author":"E Mamcarz","year":"2019","unstructured":"Mamcarz, E. et al. Lentiviral gene therapy combined with low-dose busulfan in infants with SCID-X1. N. Engl. J. Med. 380, 1525\u20131534 (2019).","journal-title":"N. Engl. J. Med."},{"key":"1236_CR169","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1038\/4401123a","volume":"440","author":"N-B Woods","year":"2006","unstructured":"Woods, N.-B., Bottero, V., Schmidt, M., Von Kalle, C. & Verma, I. M. Therapeutic gene causing lymphoma. Nature 440, 1123 (2006).","journal-title":"Nature"},{"key":"1236_CR170","doi-asserted-by":"publisher","first-page":"3132","DOI":"10.1172\/JCI35700","volume":"118","author":"S Hacein-Bey-Abina","year":"2008","unstructured":"Hacein-Bey-Abina, S. et al. Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. J. Clin. Invest. 118, 3132\u20133142 (2008).","journal-title":"J. Clin. Invest."},{"key":"1236_CR171","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1089\/hum.2014.2525","volume":"25","author":"C Von Kalle","year":"2014","unstructured":"Von Kalle, C., Deichmann, A. & Schmidt, M. Vector integration and tumorigenesis. Hum. Gene Ther. 25, 475\u2013481 (2014).","journal-title":"Hum. Gene Ther."},{"key":"1236_CR172","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1126\/science.1088547","volume":"302","author":"S Hacein-Bey-Abina","year":"2003","unstructured":"Hacein-Bey-Abina, S. et al. LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-XI. Science 302, 415\u2013419 (2003).","journal-title":"Science"},{"key":"1236_CR173","doi-asserted-by":"publisher","first-page":"2002","DOI":"10.1056\/NEJMoa2027675","volume":"384","author":"DB Kohn","year":"2021","unstructured":"Kohn, D. B. et al. Autologous ex vivo lentiviral gene therapy for adenosine deaminase deficiency. N. Engl. J. Med. 384, 2002\u20132013 (2021).","journal-title":"N. Engl. J. Med."},{"key":"1236_CR174","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1172\/JCI37630","volume":"119","author":"E Montini","year":"2009","unstructured":"Montini, E. et al. The genotoxic potential of retroviral vectors is strongly modulated by vector design and integration site selection in a mouse model of HSC gene therapy. J. Clin. Investig. 119, 964\u2013975 (2009).","journal-title":"J. Clin. Investig."},{"key":"1236_CR175","doi-asserted-by":"publisher","first-page":"3097","DOI":"10.1016\/j.ymthe.2022.08.022","volume":"30","author":"DA Williams","year":"2022","unstructured":"Williams, D. A. The long road traveled in hematopoietic stem cell gene therapy. Mol. Ther. 30, 3097\u20133099 (2022).","journal-title":"Mol. Ther."},{"key":"1236_CR176","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1056\/NEJMoa2405541","volume":"391","author":"CN Duncan","year":"2024","unstructured":"Duncan, C. N. et al. Hematologic cancer after gene therapy for cerebral adrenoleukodystrophy. N. Engl. J. Med. 391, 1287\u20131301 (2024).","journal-title":"N. Engl. J. Med."},{"key":"1236_CR177","doi-asserted-by":"publisher","first-page":"1067417","DOI":"10.3389\/fimmu.2022.1067417","volume":"13","author":"J Brault","year":"2023","unstructured":"Brault, J. et al. CRISPR\u2013Cas9\u2013AAV versus lentivector transduction for genome modification of X-linked severe combined immunodeficiency hematopoietic stem cells. Front. Immunol. 13, 1067417 (2023).","journal-title":"Front. Immunol."},{"key":"1236_CR178","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42036-5","volume":"14","author":"D Allen","year":"2023","unstructured":"Allen, D. et al. CRISPR\u2013Cas9 engineering of the RAG2 locus via complete coding sequence replacement for therapeutic applications. Nat. Commun. 14, 6771 (2023).","journal-title":"Nat. Commun."},{"key":"1236_CR179","doi-asserted-by":"publisher","first-page":"1820","DOI":"10.1182\/bloodadvances.2023011766","volume":"8","author":"M Pavel-Dinu","year":"2024","unstructured":"Pavel-Dinu, M. et al. Genetically corrected RAG2-SCID human hematopoietic stem cells restore V(D)J-recombinase and rescue lymphoid deficiency. Blood Adv. 8, 1820\u20131833 (2024).","journal-title":"Blood Adv."},{"key":"1236_CR180","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1038\/s41588-018-0174-0","volume":"50","author":"CD Richardson","year":"2018","unstructured":"Richardson, C. D. et al. CRISPR\u2013Cas9 genome editing in human cells works via the Fanconi anemia pathway. Nat. Genet. 50, 1132\u20131139 (2018).","journal-title":"Nat. Genet."},{"key":"1236_CR181","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1016\/j.stem.2019.08.016","volume":"25","author":"FJ Rom\u00e1n-Rodr\u00edguez","year":"2019","unstructured":"Rom\u00e1n-Rodr\u00edguez, F. J. et al. NHEJ-mediated repair of CRISPR\u2013Cas9-induced DNA breaks efficiently corrects mutations in HSPCs from patients with Fanconi anemia. Cell Stem Cell 25, 607\u2013621 (2019).","journal-title":"Cell Stem Cell"},{"key":"1236_CR182","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.1038\/s41591-019-0550-z","volume":"25","author":"P R\u00edo","year":"2019","unstructured":"R\u00edo, P. et al. Successful engraftment of gene-corrected hematopoietic stem cells in non-conditioned patients with Fanconi anemia. Nat. Med. 25, 1396\u20131401 (2019).","journal-title":"Nat. Med."},{"key":"1236_CR183","doi-asserted-by":"publisher","first-page":"1298","DOI":"10.1038\/s41587-020-0551-y","volume":"38","author":"S Ferrari","year":"2020","unstructured":"Ferrari, S. et al. Efficient gene editing of human long-term hematopoietic stem cells validated by clonal tracking. Nat. Biotechnol. 38, 1298\u20131308 (2020).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR184","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1038\/s41586-018-0497-0","volume":"561","author":"H Lee-Six","year":"2018","unstructured":"Lee-Six, H. et al. Population dynamics of normal human blood inferred from somatic mutations. Nature 561, 473\u2013478 (2018).","journal-title":"Nature"},{"key":"1236_CR185","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1038\/nbt.3117","volume":"33","author":"SQ Tsai","year":"2015","unstructured":"Tsai, S. Q. et al. GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR\u2013Cas nucleases. Nat. Biotechnol. 33, 187\u2013198 (2015).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR186","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1126\/science.aav9023","volume":"364","author":"B Wienert","year":"2019","unstructured":"Wienert, B. et al. Unbiased detection of CRISPR off-targets in vivo using DISCOVER-Seq. Science 364, 286\u2013289 (2019).","journal-title":"Science"},{"key":"1236_CR187","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1038\/s41587-020-0555-7","volume":"38","author":"CR Lazzarotto","year":"2020","unstructured":"Lazzarotto, C. R. et al. CHANGE-seq reveals genetic and epigenetic effects on CRISPR\u2013Cas9 genome-wide activity. Nat. Biotechnol. 38, 1317\u20131327 (2020).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR188","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.1016\/j.stem.2021.02.002","volume":"28","author":"G Turchiano","year":"2021","unstructured":"Turchiano, G. et al. Quantitative evaluation of chromosomal rearrangements in gene-edited human stem cells by CAST-Seq. Cell Stem Cell 28, 1136\u20131147.e5 (2021).","journal-title":"Cell Stem Cell"},{"key":"1236_CR189","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1038\/nmeth.3284","volume":"12","author":"D Kim","year":"2015","unstructured":"Kim, D. et al. Digenome-seq: genome-wide profiling of CRISPR\u2013Cas9 off-target effects in human cells. Nat. Methods 12, 237\u2013243 (2015).","journal-title":"Nat. Methods"},{"key":"1236_CR190","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1038\/nmeth.4284","volume":"14","author":"P Cameron","year":"2017","unstructured":"Cameron, P. et al. Mapping the genomic landscape of CRISPR\u2013Cas9 cleavage. Nat. Methods 14, 600\u2013606 (2017).","journal-title":"Nat. Methods"},{"key":"1236_CR191","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1038\/s41588-022-01257-y","volume":"55","author":"S Cancellieri","year":"2023","unstructured":"Cancellieri, S. et al. Human genetic diversity alters therapeutic gene editing off-target outcomes. Nat. Genet. 55, 34\u201343 (2023).","journal-title":"Nat. Genet."},{"key":"1236_CR192","doi-asserted-by":"crossref","unstructured":"Lin, J. et al. Scalable assessment of genome editing off-targets associated with genetic variants. Preprint at bioRxiv https:\/\/www.biorxiv.org\/content\/10.110 (2024).","DOI":"10.1101\/2024.07.24.605019"},{"key":"1236_CR193","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1038\/nbt.4192","volume":"36","author":"M Kosicki","year":"2018","unstructured":"Kosicki, M. & Bradley, A. Repair of CRISPR\u2013Cas9-induced double-stranded breaks leads to large deletions and complex rearrangements. Nat. Biotechnol. 36, 765\u2013771 (2018).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR194","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1038\/s41588-021-00838-7","volume":"53","author":"M Leibowitz","year":"2021","unstructured":"Leibowitz, M. et al. Chromothripsis as an on-target consequence of CRISPR\u2013Cas9 genome editing. Nat. Genet. 53, 895\u2013905 (2021).","journal-title":"Nat. Genet."},{"key":"1236_CR195","doi-asserted-by":"publisher","first-page":"1807","DOI":"10.1038\/s41587-022-01377-0","volume":"40","author":"AD Nahmad","year":"2022","unstructured":"Nahmad, A. D. et al. Frequent aneuploidy in primary human T cells following CRISPR\u2013Cas9 cleavage. Nat. Biotechnol. 40, 1807\u20131813 (2022).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR196","doi-asserted-by":"publisher","first-page":"eabo7676","DOI":"10.1126\/sciadv.abo7676","volume":"8","author":"SH Park","year":"2022","unstructured":"Park, S. H. et al. Comprehensive analysis and accurate quantification of unintended large gene modifications induced by CRISPR\u2013Cas9 gene editing. Sci. Adv. 8, eabo7676 (2022).","journal-title":"Sci. Adv."},{"key":"1236_CR197","doi-asserted-by":"publisher","first-page":"4567","DOI":"10.1016\/j.cell.2023.08.041","volume":"186","author":"CA Tsuchida","year":"2023","unstructured":"Tsuchida, C. A. et al. Mitigation of chromosome loss in clinical CRISPR\u2013Cas9-engineered T cells. Cell 186, 4567\u20134582.e20 (2023).","journal-title":"Cell"},{"key":"1236_CR198","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1080\/19491034.2020.1742064","volume":"11","author":"S Liu","year":"2020","unstructured":"Liu, S. & Pellman, D. The coordination of nuclear envelope assembly and chromosome segregation in metazoans. Nucleus 11, 35\u201352 (2020).","journal-title":"Nucleus"},{"key":"1236_CR199","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1002\/sctm.20-0520","volume":"10","author":"HB Maganti","year":"2021","unstructured":"Maganti, H. B. et al. Persistence of CRISPR\/Cas9 gene edited hematopoietic stem cells following transplantation: a systematic review and meta-analysis of preclinical studies. Stem Cell Transl. Med. 10, 996\u20131007 (2021).","journal-title":"Stem Cell Transl. Med."},{"key":"1236_CR200","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.stem.2010.06.014","volume":"7","author":"M Mohrin","year":"2010","unstructured":"Mohrin, M. et al. Hematopoietic stem cell quiescence promotes error-prone DNA repair and mutagenesis. Cell Stem Cell 7, 174\u2013185 (2010).","journal-title":"Cell Stem Cell"},{"key":"1236_CR201","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1016\/j.celrep.2018.06.057","volume":"24","author":"FKB Lauridsen","year":"2018","unstructured":"Lauridsen, F. K. B. et al. Differences in cell cycle status underlie transcriptional heterogeneity in the HSC compartment. Cell Rep. 24, 766\u2013780 (2018).","journal-title":"Cell Rep."},{"key":"1236_CR202","doi-asserted-by":"publisher","first-page":"1614","DOI":"10.1016\/j.stemcr.2021.04.002","volume":"16","author":"CA Oedekoven","year":"2021","unstructured":"Oedekoven, C. A. et al. Hematopoietic stem cells retain functional potential and molecular identity in hibernation cultures. Stem Cell Rep. 16, 1614\u20131628 (2021).","journal-title":"Stem Cell Rep."},{"key":"1236_CR203","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13905","volume":"8","author":"A Bothmer","year":"2017","unstructured":"Bothmer, A. et al. Characterization of the interplay between DNA repair and CRISPR\/Cas9-induced DNA lesions at an endogenous locus. Nat. Commun. 8, 13905 (2017).","journal-title":"Nat. Commun."},{"key":"1236_CR204","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25154-w","volume":"12","author":"J Schimmel","year":"2021","unstructured":"Schimmel, J., Mu\u00f1oz-Subirana, N., Kool, H., van Schendel, R. & Tijsterman, M. Small tandem DNA duplications result from CST-guided Pol \u03b1-primase action at DNA break termini. Nat. Commun. 12, 4843 (2021).","journal-title":"Nat. Commun."},{"key":"1236_CR205","doi-asserted-by":"publisher","first-page":"10576","DOI":"10.1093\/nar\/gkaa764","volume":"48","author":"DY Kim","year":"2020","unstructured":"Kim, D. Y., Moon, S. B., Ko, J. H., Kim, Y. S. & Kim, D. Unbiased investigation of specificities of prime editing systems in human cells. Nucleic Acids Res. 48, 10576\u201310589 (2020).","journal-title":"Nucleic Acids Res."},{"key":"1236_CR206","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1038\/s41592-023-01859-2","volume":"20","author":"S Liang","year":"2023","unstructured":"Liang, S. et al. Genome-wide profiling of prime editor off-target sites in vitro and in vivo using PE-tag. Nat. Methods 20, 898\u2013907 (2023).","journal-title":"Nat. Methods"},{"key":"1236_CR207","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1016\/j.stem.2023.09.013","volume":"30","author":"M Kasbekar","year":"2023","unstructured":"Kasbekar, M., Mitchell, C. A., Proven, M. A. & Passegu\u00e9, E. Hematopoietic stem cells through the ages: a lifetime of adaptation to organismal demands. Cell Stem Cell 30, 1403\u20131420 (2023).","journal-title":"Cell Stem Cell"},{"key":"1236_CR208","doi-asserted-by":"publisher","first-page":"1778","DOI":"10.1038\/nm.2984","volume":"18","author":"J Huang","year":"2012","unstructured":"Huang, J., Nguyen-Mccarty, M., Hexner, E. O., Danet-Desnoyers, G. & Klein, P. S. Maintenance of hematopoietic stem cells through regulation of Wnt and mTOR pathways. Nat. Med. 18, 1778\u20131785 (2012).","journal-title":"Nat. Med."},{"key":"1236_CR209","doi-asserted-by":"publisher","first-page":"2397","DOI":"10.1084\/jem.20081297","volume":"205","author":"C Chen","year":"2008","unstructured":"Chen, C. et al. TSC-mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species. J. Exp. Med. 205, 2397\u20132408 (2008).","journal-title":"J. Exp. Med."},{"key":"1236_CR210","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1038\/nrm3772","volume":"15","author":"K Ito","year":"2014","unstructured":"Ito, K. & Suda, T. Metabolic requirements for the maintenance of self-renewing stem cells. Nat. Rev. Mol. Cell Biol. 15, 243\u2013256 (2014).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"1236_CR211","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1182\/blood.2023021426","volume":"144","author":"CS Johnson","year":"2024","unstructured":"Johnson, C. S. et al. Adaptation to ex vivo culture reduces human hematopoietic stem cell activity independently of the cell cycle. Blood 144, 729\u2013741 (2024).","journal-title":"Blood"},{"key":"1236_CR212","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1038\/s41586-024-07478-x","volume":"630","author":"J Aguad\u00e9-Gorgori\u00f3","year":"2024","unstructured":"Aguad\u00e9-Gorgori\u00f3, J. et al. MYCT1 controls environmental sensing in human haematopoietic stem cells. Nature 630, 412\u2013420 (2024).","journal-title":"Nature"},{"key":"1236_CR213","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1038\/s41586-023-05739-9","volume":"615","author":"M Sakurai","year":"2023","unstructured":"Sakurai, M. et al. Chemically defined cytokine-free expansion of human haematopoietic stem cells. Nature 615, 127\u2013133 (2023).","journal-title":"Nature"},{"key":"1236_CR214","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1038\/nrmicro2862","volume":"10","author":"D Ayinde","year":"2012","unstructured":"Ayinde, D., Casartelli, N. & Schwartz, O. Restricting HIV the SAMHD1 way: through nucleotide starvation. Nat. Rev. Microbiol. 10, 675\u2013680 (2012).","journal-title":"Nat. Rev. Microbiol."},{"key":"1236_CR215","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1016\/j.tim.2015.08.002","volume":"23","author":"E Ballana","year":"2015","unstructured":"Ballana, E. & Est\u00e9, J. A. SAMHD1: at the crossroads of cell proliferation, immune responses, and virus restriction. Trends Microbiol. 23, 680\u2013692 (2015).","journal-title":"Trends Microbiol."},{"key":"1236_CR216","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1080\/08916934.2018.1454912","volume":"51","author":"CH Mauney","year":"2018","unstructured":"Mauney, C. H. & Hollis, T. SAMHD1: recurring roles in cell cycle, viral restriction, cancer, and innate immunity. Autoimmunity 51, 96\u2013110 (2018).","journal-title":"Autoimmunity"},{"key":"1236_CR217","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1089\/hum.2016.103","volume":"27","author":"ME Bernardo","year":"2016","unstructured":"Bernardo, M. E. & Aiuti, A. The role of conditioning in hematopoietic stem-cell gene therapy. Hum. Gene Ther. 27, 741\u2013748 (2016).","journal-title":"Hum. Gene Ther."},{"key":"1236_CR218","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1089\/hum.2024.111924","volume":"35","author":"A Philippidis","year":"2024","unstructured":"Philippidis, A. Patient dies in beam trial of sickle cell disease candidate; company cites conditioning. Hum. Gene Ther. 35, 951\u2013954 (2024).","journal-title":"Hum. Gene Ther."},{"key":"1236_CR219","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1038\/nbt.3584","volume":"34","author":"R Palchaudhuri","year":"2016","unstructured":"Palchaudhuri, R. et al. Non-genotoxic conditioning for hematopoietic stem cell transplantation using a hematopoietic-cell-specific internalizing immunotoxin. Nat. Biotechnol. 34, 738\u2013745 (2016).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR220","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1126\/science.1149726","volume":"318","author":"A Czechowicz","year":"2007","unstructured":"Czechowicz, A., Kraft, D., Weissman, I. L. & Bhattacharya, D. Efficient transplantation via antibody-based clearance of hematopoietic stem cell niches. Science 318, 1296\u20131299 (2007).","journal-title":"Science"},{"key":"1236_CR221","doi-asserted-by":"publisher","first-page":"2104","DOI":"10.1182\/blood-2018-06-853879","volume":"133","author":"H-S Kown","year":"2019","unstructured":"Kown, H.-S. et al. Anti-human CD117 antibody-mediated bone marrow niche clearance in nonhuman primates and humanized NSG mice. Blood 133, 2104\u20132108 (2019).","journal-title":"Blood"},{"key":"1236_CR222","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-08201-x","volume":"10","author":"A Czechowicz","year":"2019","unstructured":"Czechowicz, A. et al. Selective hematopoietic stem cell ablation using CD117-antibody\u2013drug-conjugates enables safe and effective transplantation with immunity preservation. Nat. Commun. 10, 617 (2019).","journal-title":"Nat. Commun."},{"key":"1236_CR223","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-41153-5","volume":"14","author":"N Uchida","year":"2023","unstructured":"Uchida, N. et al. Fertility-preserving myeloablative conditioning using single-dose CD117 antibody\u2013drug conjugate in a rhesus gene therapy model. Nat. Commun. 14, 6291 (2023).","journal-title":"Nat. Commun."},{"key":"1236_CR224","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/j.stem.2024.10.014","volume":"32","author":"S Demirci","year":"2025","unstructured":"Demirci, S. et al. BCL11A +58\/+55 enhancer-editing facilitates HSPC engraftment and HbF induction in rhesus macaques conditioned with a CD45 antibody\u2013drug conjugate. Cell Stem Cell 32, 209\u2013226 (2025).","journal-title":"Cell Stem Cell"},{"key":"1236_CR225","unstructured":"US National Library of Medicine. ClinicalTrials.gov https:\/\/clinicaltrials.gov\/study\/NCT05223699 (2023)."},{"key":"1236_CR226","doi-asserted-by":"publisher","first-page":"2248","DOI":"10.1016\/j.cell.2022.04.039","volume":"185","author":"A Omer-Javed","year":"2022","unstructured":"Omer-Javed, A. et al. Mobilization-based chemotherapy-free engraftment of gene-edited human hematopoietic stem cells. Cell 185, 2248\u20132264.e21 (2022).","journal-title":"Cell"},{"key":"1236_CR227","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1534\/genetics.114.166389","volume":"197","author":"H Kim","year":"2014","unstructured":"Kim, H. et al. A Co-CRISPR strategy for efficient genome editing in Caenorhabditis elegans. Genetics 197, 1069\u20131080 (2014).","journal-title":"Genetics"},{"key":"1236_CR228","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1534\/g3.116.036723","volume":"7","author":"NS Kane","year":"2017","unstructured":"Kane, N. S., Vora, M., Varre, K. J. & Padgett, R. W. Efficient screening of CRISPR\/Cas9-induced events in Drosophila using a Co-CRISPR strategy. G3 7, 87\u201393 (2017).","journal-title":"G3"},{"key":"1236_CR229","doi-asserted-by":"publisher","first-page":"3197","DOI":"10.1534\/g3.116.032557","volume":"6","author":"D Tianfang Ge","year":"2016","unstructured":"Tianfang Ge, D., Tipping, C., Brodsky, M. H. & Zamore, P. D. Rapid screening for CRISPR-directed editing of the Drosophila genome using white coconversion. G3 6, 3197\u20133206 (2016).","journal-title":"G3"},{"key":"1236_CR230","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1038\/nmeth.4265","volume":"14","author":"D Agudelo","year":"2017","unstructured":"Agudelo, D. et al. Marker-free coselection for CRISPR-driven genome editing in human cells. Nat. Methods 14, 615\u2013620 (2017).","journal-title":"Nat. Methods"},{"key":"1236_CR231","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1038\/s41586-023-06496-5","volume":"621","author":"G Casirati","year":"2023","unstructured":"Casirati, G. et al. Epitope editing enables targeted immunotherapies for acute myeloid leukemia. Nature 621, 404\u2013414 (2023).","journal-title":"Nature"},{"key":"1236_CR232","doi-asserted-by":"publisher","first-page":"eadi1145","DOI":"10.1126\/scitranslmed.adi1145","volume":"15","author":"N Wellhausen","year":"2023","unstructured":"Wellhausen, N. et al. Epitope base editing CD45 in hematopoietic cells enables universal blood cancer immune therapy. Sci. Transl. Med. 15, eadi1145 (2023).","journal-title":"Sci. Transl. Med."},{"key":"1236_CR233","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1126\/science.ade6967","volume":"381","author":"L Breda","year":"2023","unstructured":"Breda, L. et al. In vivo hematopoietic stem cell modification by mRNA delivery. Science 381, 436\u2013443 (2023).","journal-title":"Science"},{"key":"1236_CR234","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1038\/s41565-024-01680-8","volume":"19","author":"X Lian","year":"2024","unstructured":"Lian, X. et al. Bone-marrow-homing lipid nanoparticles for genome editing in diseased and malignant haematopoietic stem cells. Nat. Nanotechnol. 19, 1409\u20131417 (2024).","journal-title":"Nat. Nanotechnol."},{"key":"1236_CR235","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/d41587-023-00016-6","volume":"42","author":"C Sheridan","year":"2024","unstructured":"Sheridan, C. The world\u2019s first CRISPR therapy is approved: who will receive it? Nat. Biotechnol. 42, 3\u20134 (2024).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR236","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1038\/d41573-023-00188-5","volume":"23","author":"A Mullard","year":"2024","unstructured":"Mullard, A. CRISPR gets the glory in landmark approval, but haemoglobin research made it possible. Nat. Rev. Drug. Discov. 23, 14\u201315 (2024).","journal-title":"Nat. Rev. Drug. Discov."},{"key":"1236_CR237","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1038\/s41573-023-00762-x","volume":"22","author":"V Madigan","year":"2023","unstructured":"Madigan, V., Zhang, F. & Dahlman, J. E. Drug delivery systems for CRISPR-based genome editors. Nat. Rev. Drug. Discov. 22, 875\u2013894 (2023).","journal-title":"Nat. Rev. Drug. Discov."},{"key":"1236_CR238","doi-asserted-by":"publisher","first-page":"3968","DOI":"10.1182\/blood.V94.12.3968","volume":"94","author":"JN Lozier","year":"1999","unstructured":"Lozier, J. N., Metzger, M. E., Donahue, R. E. & Morgan, R. A. Adenovirus-mediated expression of human coagulation factor IX in the rhesus macaque is associated with dose-limiting toxicity. Blood 94, 3968\u20133975 (1999).","journal-title":"Blood"},{"key":"1236_CR239","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1089\/hgtb.2012.243","volume":"24","author":"V Louis Jeune","year":"2013","unstructured":"Louis Jeune, V., Joergensen, J. A., Hajjar, R. J. & Weber, T. Pre-existing anti-adeno-associated virus antibodies as a challenge in AAV gene therapy. Hum. Gene Ther. Methods 24, 59\u201367 (2013).","journal-title":"Hum. Gene Ther. Methods"},{"key":"1236_CR240","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1089\/hum.2017.009","volume":"28","author":"RJ Chandler","year":"2017","unstructured":"Chandler, R. J., Sands, M. S. & Venditti, C. P. Recombinant adeno-associated viral integration and genotoxicity: insights from animal models. Hum. Gene Ther. 28, 314\u2013322 (2017).","journal-title":"Hum. Gene Ther."},{"key":"1236_CR241","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1038\/s41576-019-0205-4","volume":"21","author":"C Li","year":"2020","unstructured":"Li, C. & Samulski, R. J. Engineering adeno-associated virus vectors for gene therapy. Nat. Rev. Genet. 21, 255\u2013272 (2020).","journal-title":"Nat. Rev. Genet."},{"key":"1236_CR242","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.1038\/s41587-023-01974-7","volume":"42","author":"JA Greig","year":"2024","unstructured":"Greig, J. A. et al. Integrated vector genomes may contribute to long-term expression in primate liver after AAV administration. Nat. Biotechnol. 42, 1232\u20131242 (2024).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR243","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1056\/NEJMoa2307798","volume":"389","author":"A Lek","year":"2023","unstructured":"Lek, A. et al. Death after high-dose rAAV9 gene therapy in a patient with Duchenne\u2019s muscular dystrophy. N. Engl. J. Med. 389, 1203\u20131210 (2023).","journal-title":"N. Engl. J. Med."},{"key":"1236_CR244","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.immuni.2005.06.008","volume":"23","author":"K Karik\u00f3","year":"2005","unstructured":"Karik\u00f3, K., Buckstein, M., Ni, H. & Weissman, D. Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA. Immunity 23, 165\u2013175 (2005).","journal-title":"Immunity"},{"key":"1236_CR245","doi-asserted-by":"publisher","first-page":"2603","DOI":"10.1056\/NEJMoa2034577","volume":"383","author":"FP Polack","year":"2020","unstructured":"Polack, F. P. et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. N. Engl. J. Med. 383, 2603\u20132615 (2020).","journal-title":"N. Engl. J. Med."},{"key":"1236_CR246","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1056\/NEJMoa2035389","volume":"384","author":"LR Baden","year":"2021","unstructured":"Baden, L. R. et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N. Engl. J. Med. 384, 403\u2013416 (2021).","journal-title":"N. Engl. J. Med."},{"key":"1236_CR247","doi-asserted-by":"publisher","first-page":"12181","DOI":"10.1021\/acs.chemrev.1c00244","volume":"121","author":"Y Zhang","year":"2021","unstructured":"Zhang, Y., Sun, C., Wang, C., Jankovic, K. E. & Dong, Y. Lipids and lipid derivatives for RNA delivery. Chem. Rev. 121, 12181\u201312277 (2021).","journal-title":"Chem. Rev."},{"key":"1236_CR248","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1038\/s41565-020-0669-6","volume":"15","author":"Q Cheng","year":"2020","unstructured":"Cheng, Q. et al. Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR\u2013Cas gene editing. Nat. Nanotechnol. 15, 313\u2013320 (2020).","journal-title":"Nat. Nanotechnol."},{"key":"1236_CR249","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2109256118","volume":"118","author":"SA Dilliard","year":"2021","unstructured":"Dilliard, S. A., Cheng, Q. & Siegwart, D. J. On the mechanism of tissue-specific mRNA delivery by selective organ targeting nanoparticles. Proc. Natl Acad. Sci. USA 118, e2109256118 (2021).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1236_CR250","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1182\/blood.2022019333","volume":"142","author":"V Vavassori","year":"2023","unstructured":"Vavassori, V. et al. Lipid nanoparticles allow efficient and harmless ex vivo gene editing of human hematopoietic cells. Blood 142, 812\u2013826 (2023).","journal-title":"Blood"},{"key":"1236_CR251","doi-asserted-by":"publisher","first-page":"1422","DOI":"10.1182\/blood-2013-11-540641","volume":"123","author":"C Costa","year":"2014","unstructured":"Costa, C. et al. Mystery solved: VSV-G-LVs do not allow efficient gene transfer into unstimulated T cells, B cells, and HSCs because they lack the LDL receptor. Blood 123, 1422\u20131423 (2014).","journal-title":"Blood"},{"key":"1236_CR252","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1038\/s41587-022-01393-0","volume":"41","author":"R Chen","year":"2023","unstructured":"Chen, R. et al. Engineering circular RNA for enhanced protein production. Nat. Biotechnol. 41, 262\u2013272 (2023).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR253","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-024-02393-y","author":"H Chen","year":"2024","unstructured":"Chen, H. et al. Chemical and topological design of multicapped mRNA and capped circular RNA to augment translation. Nat. Biotechnol. https:\/\/doi.org\/10.1038\/s41587-024-02393-y (2024).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR254","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-024-02174-7","author":"H Chen","year":"2024","unstructured":"Chen, H. et al. Branched chemically modified poly(A) tails enhance the translation capacity of mRNA. Nat. Biotechnol. https:\/\/doi.org\/10.1038\/s41587-024-02174-7 (2024).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR255","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1038\/nbt.2612","volume":"31","author":"J Gilleron","year":"2013","unstructured":"Gilleron, J. et al. Image-based analysis of lipid nanoparticle-mediated siRNA delivery, intracellular trafficking and endosomal escape. Nat. Biotechnol. 31, 638\u2013646 (2013).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR256","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1038\/s41573-024-00943-2","volume":"23","author":"JR Androsavich","year":"2024","unstructured":"Androsavich, J. R. Frameworks for transformational breakthroughs in RNA-based medicines. Nat. Rev. Drug. Discov. 23, 421\u2013444 (2024).","journal-title":"Nat. Rev. Drug. Discov."},{"key":"1236_CR257","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1261\/rna.079507.122","volume":"29","author":"SF Dowdy","year":"2023","unstructured":"Dowdy, S. F. Endosomal escape of RNA therapeutics: how do we solve this rate-limiting problem? RNA 29, 396\u2013401 (2023).","journal-title":"RNA"},{"key":"1236_CR258","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1038\/nbt.2614","volume":"31","author":"G Sahay","year":"2013","unstructured":"Sahay, G. et al. Efficiency of siRNA delivery by lipid nanoparticles is limited by endocytic recycling. Nat. Biotechnol. 31, 653\u2013658 (2013).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR259","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.cell.2024.07.023","volume":"187","author":"DW Brown","year":"2024","unstructured":"Brown, D. W. et al. Safe and effective in vivo delivery of DNA and RNA using proteolipid vehicles. Cell 187, 1\u201319 (2024).","journal-title":"Cell"},{"key":"1236_CR260","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1038\/s41587-023-01756-1","volume":"42","author":"Z Zhang","year":"2024","unstructured":"Zhang, Z. et al. Efficient engineering of human and mouse primary cells using peptide-assisted genome editing. Nat. Biotechnol. 42, 305\u2013315 (2024).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR261","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1038\/s41551-023-01032-2","volume":"7","author":"DV Foss","year":"2023","unstructured":"Foss, D. V. et al. Peptide-mediated delivery of CRISPR enzymes for the efficient editing of primary human lymphocytes. Nat. Biomed. Eng. 7, 647\u2013660 (2023).","journal-title":"Nat. Biomed. Eng."},{"key":"1236_CR262","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1038\/gt.2016.27","volume":"23","author":"JG Choi","year":"2016","unstructured":"Choi, J. G. et al. Lentivirus pre-packed with Cas9 protein for safer gene editing. Gene Ther. 23, 627\u2013633 (2016).","journal-title":"Gene Ther."},{"key":"1236_CR263","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1016\/j.omtn.2018.05.010","volume":"12","author":"C Montagna","year":"2018","unstructured":"Montagna, C. et al. VSV-G-enveloped vesicles for traceless delivery of CRISPR\u2013Cas9. Mol. Ther. Nucleic Acids 12, 453\u2013462 (2018).","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"1236_CR264","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz605","volume":"47","author":"P Lyu","year":"2019","unstructured":"Lyu, P., Javidi-Parsijani, P., Atala, A. & Lu, B. Delivering Cas9\/sgRNA ribonucleoprotein (RNP) by lentiviral capsid-based bionanoparticles for efficient \u2018hit-and-run\u2019 genome editing. Nucleic Acids Res. 47, e99 (2019).","journal-title":"Nucleic Acids Res."},{"key":"1236_CR265","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07845-z","volume":"10","author":"PE Mangeot","year":"2019","unstructured":"Mangeot, P. E. et al. Genome editing in primary cells and in vivo using viral-derived nanoblades loaded with Cas9\u2013sgRNA ribonucleoproteins. Nat. Commun. 10, 45 (2019).","journal-title":"Nat. Commun."},{"key":"1236_CR266","doi-asserted-by":"publisher","first-page":"109207","DOI":"10.1016\/j.celrep.2021.109207","volume":"35","author":"JR Hamilton","year":"2021","unstructured":"Hamilton, J. R. et al. Targeted delivery of CRISPR\u2013Cas9 and transgenes enables complex immune cell engineering. Cell Rep. 35, 109207 (2021).","journal-title":"Cell Rep."},{"key":"1236_CR267","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.cell.2021.12.021","volume":"185","author":"S Banskota","year":"2022","unstructured":"Banskota, S. et al. Engineered virus-like particles for efficient in vivo delivery of therapeutic proteins. Cell 185, 1\u201316 (2022).","journal-title":"Cell"},{"key":"1236_CR268","doi-asserted-by":"publisher","first-page":"1526","DOI":"10.1038\/s41587-023-02078-y","volume":"42","author":"M An","year":"2024","unstructured":"An, M. et al. Engineered virus-like particles for transient delivery of prime editor ribonucleoprotein complexes in vivo. Nat. Biotechnol. 42, 1526\u20131537 (2024).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR269","doi-asserted-by":"publisher","first-page":"7306","DOI":"10.1073\/pnas.1214441110","volume":"110","author":"D Finkelshtein","year":"2013","unstructured":"Finkelshtein, D., Werman, A., Novick, D., Barak, S. & Rubinstein, M. LDL receptor and its family members serve as the cellular receptors for vesicular stomatitis virus. Proc. Natl Acad. Sci. USA 110, 7306\u20137311 (2013).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1236_CR270","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1182\/blood-2014-02-558163","volume":"124","author":"A Girard-Gagnepain","year":"2014","unstructured":"Girard-Gagnepain, A. et al. Baboon envelope pseudotyped LVs outperform VSV-G-LVs for gene transfer into early-cytokine-stimulated and resting HSCs. Blood 124, 1221\u20131231 (2014).","journal-title":"Blood"},{"key":"1236_CR271","doi-asserted-by":"publisher","first-page":"1684","DOI":"10.1038\/s41587-023-02085-z","volume":"42","author":"JR Hamilton","year":"2024","unstructured":"Hamilton, J. R. et al. In vivo human T cell engineering with enveloped delivery vehicles. Nat. Biotechnol. 42, 1684\u20131692 (2024).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR272","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1038\/s41551-021-00842-6","volume":"6","author":"T Car","year":"2022","unstructured":"Car, T. et al. Rapid manufacturing of non-activated potent CAR T cells. Nat. Biomed. Eng. 6, 118\u2013128 (2022).","journal-title":"Nat. Biomed. Eng."},{"key":"1236_CR273","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.ymthe.2023.11.020","volume":"32","author":"E Valeri","year":"2024","unstructured":"Valeri, E. et al. Removal of innate immune barriers allows efficient transduction of quiescent human hematopoietic stem cells. Mol. Ther. 32, 124\u2013139 (2024).","journal-title":"Mol. Ther."},{"key":"1236_CR274","doi-asserted-by":"publisher","first-page":"eadj5465","DOI":"10.1126\/sciimmunol.adj5465","volume":"9","author":"P Zhang","year":"2024","unstructured":"Zhang, P. et al. Schlafen 11 triggers innate immune responses through its ribonuclease activity upon detection of single-stranded DNA. Sci. Immunol. 9, eadj5465 (2024).","journal-title":"Sci. Immunol."},{"key":"1236_CR275","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-024-02405-x","author":"P Liu","year":"2024","unstructured":"Liu, P. et al. Increasing intracellular dNTP levels improves prime editing efficiency. Nat. Biotechnol. https:\/\/doi.org\/10.1038\/s41587-024-02405-x (2024).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR276","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-01947-w","author":"B Liu","year":"2023","unstructured":"Liu, B. et al. Targeted genome editing with a DNA-dependent DNA polymerase and exogenous DNA-containing templates. Nat. Biotechnol. https:\/\/doi.org\/10.1038\/s41587-023-01947-w (2023).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR277","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-024-02324-x","author":"JF da Silva","year":"2024","unstructured":"da Silva, J. F. et al. Click editing enables programmable genome writing using DNA polymerases and HUH endonucleases. Nat. Biotechnol. https:\/\/doi.org\/10.1038\/s41587-024-02324-x (2024).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR278","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1021\/acscentsci.1c00197","volume":"7","author":"KD Nance","year":"2021","unstructured":"Nance, K. D. & Meier, J. L. Modifications in an emergency: the role of N1-methylpseudouridine in COVID-19 vaccines. ACS Cent. Sci. 7, 748\u2013756 (2021).","journal-title":"ACS Cent. Sci."},{"key":"1236_CR279","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-024-02306-z","author":"JE McGee","year":"2024","unstructured":"McGee, J. E. et al. Complete substitution with modified nucleotides suppresses the early interferon response and increases the potency of self-amplifying RNA. Nat. Biotechnol. https:\/\/doi.org\/10.1038\/s41587-024-02306-z (2024).","journal-title":"Nat. Biotechnol."},{"key":"1236_CR280","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1097\/00000441-194804000-00008","volume":"215","author":"J Watson","year":"1948","unstructured":"Watson, J. The significance of the paucity of sickle cells in newborn Negro infants. Am. J. Med. Sci. 215, 419\u2013423 (1948).","journal-title":"Am. J. Med. Sci."},{"key":"1236_CR281","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1182\/blood-2019-126048","volume":"134","author":"S Lessard","year":"2019","unstructured":"Lessard, S. et al. Zinc finger nuclease-mediated disruption of the BCL11A erythroid enhancer results in enriched biallelic editing, increased fetal hemoglobin, and reduced sickling in erythroid cells derived from sickle cell disease patients. Blood 134, 974\u2013974 (2019).","journal-title":"Blood"},{"key":"1236_CR282","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1056\/NEJMoa2215643","volume":"389","author":"A Sharma","year":"2023","unstructured":"Sharma, A. et al. CRISPR\u2013Cas9 editing of the HBG1 and HBG2 promoters to treat sickle cell disease. N. Engl. J. Med. 389, 820\u2013832 (2023).","journal-title":"N. Engl. J. Med."},{"key":"1236_CR283","doi-asserted-by":"publisher","first-page":"4636","DOI":"10.1182\/blood-2019-130256","volume":"134","author":"E De Dreuzy","year":"2019","unstructured":"De Dreuzy, E. et al. EDIT-301: an experimental autologous cell therapy comprising Cas12a-RNP modified mPB-CD34+ cells for the potential treatment of SCD. Blood 134, 4636\u20134636 (2019).","journal-title":"Blood"}],"container-title":["Nature Reviews Drug Discovery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41573-025-01236-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41573-025-01236-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41573-025-01236-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T13:02:50Z","timestamp":1764334970000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41573-025-01236-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,14]]},"references-count":283,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["1236"],"URL":"https:\/\/doi.org\/10.1038\/s41573-025-01236-y","relation":{},"ISSN":["1474-1776","1474-1784"],"issn-type":[{"value":"1474-1776","type":"print"},{"value":"1474-1784","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,14]]},"assertion":[{"value":"3 June 2025","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 July 2025","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"S.L. and D.E.B. are inventors on patent applications related to therapeutic genome editing.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}