{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:07:03Z","timestamp":1792649223780,"version":"4.5.0"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"7843","license":[{"start":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T00:00:00Z","timestamp":1609891200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T00:00:00Z","timestamp":1609891200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2021,1,28]]},"DOI":"10.1038\/s41586-020-03086-7","type":"journal-article","created":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T17:13:23Z","timestamp":1609953203000},"page":"608-614","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":470,"title":["In vivo base editing rescues Hutchinson\u2013Gilford progeria syndrome in mice"],"prefix":"10.1038","volume":"589","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2814-4412","authenticated-orcid":false,"given":"Luke W.","family":"Koblan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6603-1833","authenticated-orcid":false,"given":"Michael R.","family":"Erdos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8012-2440","authenticated-orcid":false,"given":"Christopher","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0563-5289","authenticated-orcid":false,"given":"Wayne A.","family":"Cabral","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8061-7953","authenticated-orcid":false,"given":"Jonathan M.","family":"Levy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng-Mei","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2577-5377","authenticated-orcid":false,"given":"Urraca L.","family":"Tavarez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay M.","family":"Davison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yantenew G.","family":"Gete","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory A.","family":"Newby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean P.","family":"Doherty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8483-1156","authenticated-orcid":false,"given":"Narisu","family":"Narisu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanhu","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad","family":"Krilow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9155-090X","authenticated-orcid":false,"given":"Charles Y.","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie B.","family":"Gordon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5806-2939","authenticated-orcid":false,"given":"Kan","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1023-7410","authenticated-orcid":false,"given":"Francis S.","family":"Collins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0359-6167","authenticated-orcid":false,"given":"Jonathan D.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9943-7557","authenticated-orcid":false,"given":"David R.","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,6]]},"reference":[{"key":"3086_CR1","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/nature01629","volume":"423","author":"M Eriksson","year":"2003","unstructured":"Eriksson, M. et al. Recurrent de novo point mutations in lamin A cause Hutchinson\u2013Gilford progeria syndrome. Nature 423, 293\u2013298 (2003).","journal-title":"Nature"},{"key":"3086_CR2","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1126\/science.1084125","volume":"300","author":"A De Sandre-Giovannoli","year":"2003","unstructured":"De Sandre-Giovannoli, A. et al. Lamin A truncation in Hutchinson\u2013Gilford progeria. Science 300, 2055 (2003).","journal-title":"Science"},{"key":"3086_CR3","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1161\/CIRCULATIONAHA.113.008285","volume":"130","author":"LB Gordon","year":"2014","unstructured":"Gordon, L. B. et al. Impact of farnesylation inhibitors on survival in Hutchinson\u2013Gilford progeria syndrome. Circulation 130, 27\u201334 (2014).","journal-title":"Circulation"},{"key":"3086_CR4","unstructured":"Gordon, L. B., Brown, W. T. & Collins, F. S. Hutchinson\u2013Gilford Progeria Syndrome (GeneReviews, 2019)."},{"key":"3086_CR5","doi-asserted-by":"crossref","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":"3086_CR6","doi-asserted-by":"crossref","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":"3086_CR7","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1161\/ATVBAHA.110.209460","volume":"30","author":"M Olive","year":"2010","unstructured":"Olive, M. et al. Cardiovascular pathology in Hutchinson\u2013Gilford progeria: correlation with the vascular pathology of aging. Arterioscler. Thromb. Vasc. Biol. 30, 2301\u20132309 (2010).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"3086_CR8","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1161\/HYPERTENSIONAHA.111.180919","volume":"59","author":"M Gerhard-Herman","year":"2012","unstructured":"Gerhard-Herman, M. et al. Mechanisms of premature vascular aging in children with Hutchinson\u2013Gilford progeria syndrome. Hypertension 59, 92\u201397 (2012).","journal-title":"Hypertension"},{"key":"3086_CR9","doi-asserted-by":"crossref","first-page":"E7250","DOI":"10.1073\/pnas.1603754113","volume":"113","author":"J Rivera-Torres","year":"2016","unstructured":"Rivera-Torres, J. et al. Cardiac electrical defects in progeroid mice and Hutchinson\u2013Gilford progeria syndrome patients with nuclear lamina alterations. Proc. Natl Acad. Sci. USA 113, E7250\u2013E7259 (2016).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"3086_CR10","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1001\/jamacardio.2017.5235","volume":"3","author":"A Prakash","year":"2018","unstructured":"Prakash, A. et al. Cardiac abnormalities in patients with Hutchinson\u2013Gilford progeria syndrome. JAMA Cardiol. 3, 326\u2013334 (2018).","journal-title":"JAMA Cardiol."},{"key":"3086_CR11","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S1054-8807(98)00023-4","volume":"8","author":"WE Stehbens","year":"1999","unstructured":"Stehbens, W. E., Wakefield, S. J., Gilbert-Barness, E., Olson, R. E. & Ackerman, J. Histological and ultrastructural features of atherosclerosis in progeria. Cardiovasc. Pathol. 8, 29\u201339 (1999).","journal-title":"Cardiovasc. Pathol."},{"key":"3086_CR12","doi-asserted-by":"crossref","first-page":"16666","DOI":"10.1073\/pnas.1202529109","volume":"109","author":"LB Gordon","year":"2012","unstructured":"Gordon, L. B. et al. Clinical trial of a farnesyltransferase inhibitor in children with Hutchinson\u2013Gilford progeria syndrome. Proc. Natl Acad. Sci. USA 109, 16666\u201316671 (2012).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"3086_CR13","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1038\/nrg1906","volume":"7","author":"BC Capell","year":"2006","unstructured":"Capell, B. C. & Collins, F. S. Human laminopathies: nuclei gone genetically awry. Nat. Rev. Genet. 7, 940\u2013952 (2006).","journal-title":"Nat. Rev. Genet."},{"key":"3086_CR14","volume":"19","author":"W-F Lai","year":"2020","unstructured":"Lai, W.-F. & Wong, W.-T. Progress and trends in the development of therapies for Hutchinson\u2013Gilford progeria syndrome. Aging Cell 19, e13175 (2020).","journal-title":"Aging Cell"},{"key":"3086_CR15","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1038\/s41591-019-0343-4","volume":"25","author":"E Beyret","year":"2019","unstructured":"Beyret, E. et al. Single-dose CRISPR\u2013Cas9 therapy extends lifespan of mice with Hutchinson\u2013Gilford progeria syndrome. Nat. Med. 25, 419\u2013422 (2019).","journal-title":"Nat. Med."},{"key":"3086_CR16","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/s41591-018-0338-6","volume":"25","author":"O Santiago-Fern\u00e1ndez","year":"2019","unstructured":"Santiago-Fern\u00e1ndez, O. et al. Development of a CRISPR\/Cas9-based therapy for Hutchinson\u2013Gilford progeria syndrome. Nat. Med. 25, 423\u2013426 (2019).","journal-title":"Nat. Med."},{"key":"3086_CR17","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1038\/s41422-019-0213-0","volume":"29","author":"K Suzuki","year":"2019","unstructured":"Suzuki, K. et al. Precise in vivo genome editing via single homology arm donor mediated intron-targeting gene integration for genetic disease correction. Cell Res. 29, 804\u2013819 (2019).","journal-title":"Cell Res."},{"key":"3086_CR18","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1038\/nm1204","volume":"11","author":"P Scaffidi","year":"2005","unstructured":"Scaffidi, P. & Misteli, T. Reversal of the cellular phenotype in the premature aging disease Hutchinson\u2013Gilford progeria syndrome. Nat. Med. 11, 440\u2013445 (2005).","journal-title":"Nat. Med."},{"key":"3086_CR19","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1146\/annurev-biophys-062215-010822","volume":"46","author":"F Jiang","year":"2017","unstructured":"Jiang, F. & Doudna, J. A. CRISPR\u2013Cas9 structures and mechanisms. Annu. Rev. Biophys. 46, 505\u2013529 (2017).","journal-title":"Annu. Rev. Biophys."},{"key":"3086_CR20","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/nbt.2673","volume":"31","author":"V Pattanayak","year":"2013","unstructured":"Pattanayak, V. et al. High-throughput profiling of off-target DNA cleavage reveals RNA-programmed Cas9 nuclease specificity. Nat. Biotechnol. 31, 839\u2013843 (2013).","journal-title":"Nat. Biotechnol."},{"key":"3086_CR21","doi-asserted-by":"crossref","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":"3086_CR22","doi-asserted-by":"crossref","first-page":"3250","DOI":"10.1073\/pnas.0600012103","volume":"103","author":"R Varga","year":"2006","unstructured":"Varga, R. et al. Progressive vascular smooth muscle cell defects in a mouse model of Hutchinson\u2013Gilford progeria syndrome. Proc. Natl Acad. Sci. USA 103, 3250\u20133255 (2006).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"3086_CR23","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/s41587-019-0134-y","volume":"37","author":"TP Huang","year":"2019","unstructured":"Huang, T. P. et al. Circularly permuted and PAM-modified Cas9 variants broaden the targeting scope of base editors. Nat. Biotechnol. 37, 626\u2013631 (2019).","journal-title":"Nat. Biotechnol."},{"key":"3086_CR24","doi-asserted-by":"crossref","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\u2013846 (2018).","journal-title":"Nat. Biotechnol."},{"key":"3086_CR25","doi-asserted-by":"crossref","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":"3086_CR26","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/nmeth.4278","volume":"14","author":"SQ Tsai","year":"2017","unstructured":"Tsai, S. Q. et al. CIRCLE-seq: a highly sensitive in vitro screen for genome-wide CRISPR\u2013Cas9 nuclease off-targets. Nat. Methods 14, 607\u2013614 (2017).","journal-title":"Nat. Methods"},{"key":"3086_CR27","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/s41576-018-0006-1","volume":"19","author":"E Eisenberg","year":"2018","unstructured":"Eisenberg, E. & Levanon, E. Y. A-to-I RNA editing\u2014immune protector and transcriptome diversifier. Nat. Rev. Genet. 19, 473\u2013490 (2018).","journal-title":"Nat. Rev. Genet."},{"key":"3086_CR28","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/s41551-019-0501-5","volume":"4","author":"JM Levy","year":"2020","unstructured":"Levy, J. M. et al. Cytosine and adenine base editing of the brain, liver, retina, heart and skeletal muscle of mice via adeno-associated viruses. Nat. Biomed. Eng. 4, 97\u2013110 (2020).","journal-title":"Nat. Biomed. Eng."},{"key":"3086_CR29","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1038\/s41591-018-0209-1","volume":"24","author":"L Villiger","year":"2018","unstructured":"Villiger, L. et al. Treatment of a metabolic liver disease by in vivo genome base editing in adult mice. Nat. Med. 24, 1519\u20131525 (2018).","journal-title":"Nat. Med."},{"key":"3086_CR30","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1038\/mt.2008.76","volume":"16","author":"C Zincarelli","year":"2008","unstructured":"Zincarelli, C., Soltys, S., Rengo, G. & Rabinowitz, J. E. Analysis of AAV serotypes 1-9 mediated gene expression and tropism in mice after systemic injection. Mol. Ther. 16, 1073\u20131080 (2008).","journal-title":"Mol. Ther."},{"key":"3086_CR31","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.ymthe.2006.03.014","volume":"14","author":"K Inagaki","year":"2006","unstructured":"Inagaki, K. et al. Robust systemic transduction with AAV9 vectors in mice: efficient global cardiac gene transfer superior to that of AAV8. Mol. Ther. 14, 45\u201353 (2006).","journal-title":"Mol. Ther."},{"key":"3086_CR32","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1038\/sj.gt.3303029","volume":"14","author":"B Bostick","year":"2007","unstructured":"Bostick, B., Ghosh, A., Yue, Y., Long, C. & Duan, D. Systemic AAV-9 transduction in mice is influenced by animal age but not by the route of administration. Gene Ther. 14, 1605\u20131609 (2007).","journal-title":"Gene Ther."},{"key":"3086_CR33","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1089\/hum.2011.183","volume":"23","author":"L Wang","year":"2012","unstructured":"Wang, L., Wang, H., Bell, P., McMenamin, D. & Wilson, J. M. Hepatic gene transfer in neonatal mice by adeno-associated virus serotype 8 vector. Hum. Gene Ther. 23, 533\u2013539 (2012).","journal-title":"Hum. Gene Ther."},{"key":"3086_CR34","doi-asserted-by":"crossref","first-page":"14082","DOI":"10.1073\/pnas.93.24.14082","volume":"93","author":"PD Kessler","year":"1996","unstructured":"Kessler, P. D. et al. Gene delivery to skeletal muscle results in sustained expression and systemic delivery of a therapeutic protein. Proc. Natl Acad. Sci. USA 93, 14082\u201314087 (1996).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"3086_CR35","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1056\/NEJMoa1407309","volume":"371","author":"AC Nathwani","year":"2014","unstructured":"Nathwani, A. C. et al. Long-term safety and efficacy of factor IX gene therapy in hemophilia B. N. Engl. J. Med. 371, 1994\u20132004 (2014).","journal-title":"N. Engl. J. Med."},{"key":"3086_CR36","unstructured":"Hagan, C. When are mice considered old? The Jackson Laboratory https:\/\/www.jax.org\/news-and-insights\/jax-blog\/2017\/november\/when-are-mice-considered-old (2017)."},{"key":"3086_CR37","doi-asserted-by":"crossref","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":"3086_CR38","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1038\/mt.2016.47","volume":"24","author":"J-C Nault","year":"2016","unstructured":"Nault, J.-C. et al. Wild-type AAV insertions in hepatocellular carcinoma do not inform debate over genotoxicity risk of vectorized AAV. Mol. Ther. 24, 660\u2013661 (2016).","journal-title":"Mol. Ther."},{"key":"3086_CR39","doi-asserted-by":"crossref","first-page":"7713","DOI":"10.1007\/s13277-015-4606-5","volume":"37","author":"D Geng","year":"2016","unstructured":"Geng, D., Zhao, W., Feng, Y. & Liu, J. Overexpression of Rab25 promotes hepatocellular carcinoma cell proliferation and invasion. Tumour Biol. 37, 7713\u20137718 (2016).","journal-title":"Tumour Biol."},{"key":"3086_CR40","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1038\/sj.gt.3301541","volume":"8","author":"A Donsante","year":"2001","unstructured":"Donsante, A. et al. Observed incidence of tumorigenesis in long-term rodent studies of rAAV vectors. Gene Ther. 8, 1343\u20131346 (2001).","journal-title":"Gene Ther."},{"key":"3086_CR41","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1126\/science.1142658","volume":"317","author":"A Donsante","year":"2007","unstructured":"Donsante, A. et al. AAV vector integration sites in mouse hepatocellular carcinoma. Science 317, 477 (2007).","journal-title":"Science"},{"key":"3086_CR42","doi-asserted-by":"crossref","first-page":"S83","DOI":"10.1016\/j.ymthe.2006.08.241","volume":"13","author":"JE Embury","year":"2006","unstructured":"Embury, J. E., Charron, C. C., Poirier, A. E. & Zori, A. Long term portal vein administration of AAV-WPRE vector results in increased incidence of neoplastic disease and hepatic pathology. Mol. Ther. 13, S83 (2006).","journal-title":"Mol. Ther."},{"key":"3086_CR43","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/978-1-61779-370-7_6","volume":"807","author":"MS Sands","year":"2011","unstructured":"Sands, M. S. AAV-mediated liver-directed gene therapy. Methods Mol. Biol. 807, 141\u2013157 (2011).","journal-title":"Methods Mol. Biol."},{"key":"3086_CR44","doi-asserted-by":"crossref","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 enhanced Cas domain compatibility and activity. Nat. Biotechnol. 38, 883\u2013891 (2020).","journal-title":"Nat. Biotechnol."},{"key":"3086_CR45","doi-asserted-by":"crossref","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":"3086_CR46","doi-asserted-by":"crossref","first-page":"106ra107","DOI":"10.1126\/scitranslmed.3002847","volume":"3","author":"FG Osorio","year":"2011","unstructured":"Osorio, F. G. et al. Splicing-directed therapy in a new mouse model of human accelerated aging. Sci. Transl. Med. 3, 106ra107 (2011).","journal-title":"Sci. Transl. Med."},{"key":"3086_CR47","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0205878","volume":"13","author":"J Mateos","year":"2018","unstructured":"Mateos, J. et al. Next-generation sequencing and quantitative proteomics of Hutchinson\u2013Gilford progeria syndrome-derived cells point to a role of nucleotide metabolism in premature aging. PloS One 13, e0205878 (2018).","journal-title":"PloS One"},{"key":"3086_CR48","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/nbt.3437","volume":"34","author":"JG Doench","year":"2016","unstructured":"Doench, J. G. et al. Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR\u2013Cas9. Nat. Biotechnol. 34, 184\u2013191 (2016).","journal-title":"Nat. Biotechnol."},{"key":"3086_CR49","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1038\/nmeth.3047","volume":"11","author":"NE Sanjana","year":"2014","unstructured":"Sanjana, N. E., Shalem, O. & Zhang, F. Improved vectors and genome-wide libraries for CRISPR screening. Nat. Methods 11, 783\u2013784 (2014).","journal-title":"Nat. Methods"},{"key":"3086_CR50","volume":"40","author":"D Wu","year":"2012","unstructured":"Wu, D. & Smyth, G. K. Camera: a competitive gene set test accounting for inter-gene correlation. Nucleic Acids Res. 40, e133 (2012).","journal-title":"Nucleic Acids Res."},{"key":"3086_CR51","first-page":"89ra58","volume":"3","author":"K Cao","year":"2011","unstructured":"Cao, K. et al. Rapamycin reverses cellular phenotypes and enhances mutant protein clearance in Hutchinson\u2013Gilford progeria syndrome cells. Sci. Transl. Med. 3, 89ra58 (2011).","journal-title":"Sci. Transl. Med."},{"key":"3086_CR52","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1093\/bioinformatics\/btw354","volume":"32","author":"P Ewels","year":"2016","unstructured":"Ewels, P., Magnusson, M., Lundin, S. & K\u00e4ller, M. MultiQC: summarize analysis results for multiple tools and samples in a single report. Bioinformatics 32, 3047\u20133048 (2016).","journal-title":"Bioinformatics"},{"key":"3086_CR53","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1006\/geno.1998.5693","volume":"58","author":"E Frengen","year":"1999","unstructured":"Frengen, E. et al. A modular, positive selection bacterial artificial chromosome vector with multiple cloning sites. Genomics 58, 250\u2013253 (1999).","journal-title":"Genomics"},{"key":"3086_CR54","doi-asserted-by":"crossref","unstructured":"DuBose, A. J. et al. Use of microarray hybrid capture and next-generation sequencing to identify the anatomy of a transgene. Nucleic Acids Res. 41, e70","DOI":"10.1093\/nar\/gks1463"},{"key":"3086_CR55","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","volume":"25","author":"H Li","year":"2009","unstructured":"Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows\u2013Wheeler transform. Bioinformatics 25, 1754\u20131760 (2009).","journal-title":"Bioinformatics"},{"key":"3086_CR56","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","volume":"25","author":"H Li","year":"2009","unstructured":"Li, H. et al. The Sequence Alignment\/Map format and SAMtools. Bioinformatics 25, 2078\u20132079 (2009).","journal-title":"Bioinformatics"},{"key":"3086_CR57","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1093\/bioinformatics\/btq033","volume":"26","author":"AR Quinlan","year":"2010","unstructured":"Quinlan, A. R. & Hall, I. M. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841\u2013842 (2010).","journal-title":"Bioinformatics"},{"key":"3086_CR58","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1093\/bioinformatics\/btv098","volume":"31","author":"A Tarasov","year":"2015","unstructured":"Tarasov, A., Vilella, A. J., Cuppen, E., Nijman, I. J. & Prins, P. Sambamba: fast processing of NGS alignment formats. Bioinformatics 31, 2032\u20132034 (2015).","journal-title":"Bioinformatics"},{"key":"3086_CR59","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1101\/gr.107524.110","volume":"20","author":"A McKenna","year":"2010","unstructured":"McKenna, A. et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20, 1297\u20131303 (2010).","journal-title":"Genome Res."},{"key":"3086_CR60","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/ng.806","volume":"43","author":"MA DePristo","year":"2011","unstructured":"DePristo, M. A. et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat. Genet. 43, 491\u2013498 (2011).","journal-title":"Nat. Genet."},{"key":"3086_CR61","doi-asserted-by":"crossref","first-page":"11.10.1","DOI":"10.1002\/0471250953.bi1110s43","volume":"43","author":"GA Van der Auwera","year":"2013","unstructured":"Van der Auwera, G. A. et al. From FastQ data to high confidence variant calls: the Genome Analysis Toolkit best practices pipeline. Curr. Protoc. Bioinformatics 43, 11.10.1\u201311.10.33 (2013).","journal-title":"Curr. Protoc. Bioinformatics"},{"key":"3086_CR62","volume":"38","author":"K Wang","year":"2010","unstructured":"Wang, K., Li, M. & Hakonarson, H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 38, e164 (2010).","journal-title":"Nucleic Acids Res."},{"key":"3086_CR63","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1038\/s41568-018-0060-1","volume":"18","author":"Z Sondka","year":"2018","unstructured":"Sondka, Z. et al. The COSMIC Cancer Gene Census: describing genetic dysfunction across all human cancers. Nat. Rev. Cancer 18, 696\u2013705 (2018).","journal-title":"Nat. Rev. Cancer"},{"key":"3086_CR64","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1038\/nmeth.2688","volume":"10","author":"JD Buenrostro","year":"2013","unstructured":"Buenrostro, J. D., Giresi, P. G., Zaba, L. C., Chang, H. Y. & Greenleaf, W. J. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 10, 1213\u20131218 (2013).","journal-title":"Nat. Methods"}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/s41586-020-03086-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41586-020-03086-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41586-020-03086-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T02:25:00Z","timestamp":1697509500000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41586-020-03086-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,6]]},"references-count":64,"journal-issue":{"issue":"7843","published-print":{"date-parts":[[2021,1,28]]}},"alternative-id":["3086"],"URL":"https:\/\/doi.org\/10.1038\/s41586-020-03086-7","relation":{},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,6]]},"assertion":[{"value":"9 June 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 November 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"D.R.L. is a co-founder of Beam Therapeutics, Prime Medicine, Pairwise Plants and Editas Medicine, companies that use genome editing. The remaining authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}