{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T15:12:22Z","timestamp":1788361942897,"version":"build-2803163510"},"reference-count":235,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,11,27]],"date-time":"2022-11-27T00:00:00Z","timestamp":1669507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The tremendous evolution of genome-editing tools in the last two decades has provided innovative and effective approaches for gene therapy of congenital and acquired diseases. Zinc-finger nucleases (ZFNs), transcription activator- like effector nucleases (TALENs) and CRISPR-Cas9 have been already applied by ex vivo hematopoietic stem cell (HSC) gene therapy in genetic diseases (i.e., Hemoglobinopathies, Fanconi anemia and hereditary Immunodeficiencies) as well as infectious diseases (i.e., HIV), and the recent development of CRISPR-Cas9-based systems using base and prime editors as well as epigenome editors has provided safer tools for gene therapy. The ex vivo approach for gene addition or editing of HSCs, however, is complex, invasive, technically challenging, costly and not free of toxicity. In vivo gene addition or editing promise to transform gene therapy from a highly sophisticated strategy to a \u201cuser-friendly\u2019 approach to eventually become a broadly available, highly accessible and potentially affordable treatment modality. In the present review article, based on the lessons gained by more than 3 decades of ex vivo HSC gene therapy, we discuss the concept, the tools, the progress made and the challenges to clinical translation of in vivo HSC gene editing.<\/jats:p>","DOI":"10.3390\/genes13122222","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T04:01:33Z","timestamp":1669608093000},"page":"2222","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["In Vivo Hematopoietic Stem Cell Genome Editing: Perspectives and Limitations"],"prefix":"10.3390","volume":"13","author":[{"given":"Nikoletta","family":"Psatha","sequence":"first","affiliation":[{"name":"Department of Genetics, Development and Molecular Biology, School of Biology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiriaki","family":"Paschoudi","sequence":"additional","affiliation":[{"name":"Department of Genetics, Development and Molecular Biology, School of Biology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"},{"name":"Gene and Cell Therapy Center, Hematology Clinic, George Papanikolaou Hospital, Exokhi, 57010 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5385-8738","authenticated-orcid":false,"given":"Anastasia","family":"Papadopoulou","sequence":"additional","affiliation":[{"name":"Gene and Cell Therapy Center, Hematology Clinic, George Papanikolaou Hospital, Exokhi, 57010 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelia","family":"Yannaki","sequence":"additional","affiliation":[{"name":"Gene and Cell Therapy Center, Hematology Clinic, George Papanikolaou Hospital, Exokhi, 57010 Thessaloniki, Greece"},{"name":"Department of Hematology, School of Medicine, University of Washington, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1038\/nrm2351","article-title":"Regulation of DNA Repair throughout the Cell Cycle","volume":"9","author":"Branzei","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3683","DOI":"10.1093\/nar\/gkh703","article-title":"Conservative Homologous Recombination Preferentially Repairs DNA Double-Strand Breaks in the S Phase of the Cell Cycle in Human Cells","volume":"32","author":"Helleday","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ho, B.X., Loh, S.J.H., Chan, W.K., and Soh, B.S. (2018). In Vivo Genome Editing as a Therapeutic Approach. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19092721"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1089\/hum.2021.013","article-title":"CRISPR\/Cas-Dependent and Nuclease-Free In Vivo Therapeutic Gene Editing","volume":"32","author":"Dasgupta","year":"2021","journal-title":"Hum. Gene Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"17071","DOI":"10.1038\/cddiscovery.2017.71","article-title":"Zinc-Finger Proteins in Health and Disease","volume":"3","author":"Cassandri","year":"2017","journal-title":"Cell Death Discov."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.semcdb.2020.09.003","article-title":"DNA Double-Strand Break Repair: Putting Zinc Fingers on the Sore Spot","volume":"113","author":"Singh","year":"2021","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2597","DOI":"10.1182\/blood-2014-12-615948","article-title":"Correction of the Sickle Cell Disease Mutation in Human Hematopoietic Stem\/Progenitor Cells","volume":"125","author":"Hoban","year":"2015","journal-title":"Blood"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2338","DOI":"10.1182\/blood-2016-08-736249","article-title":"Strict in Vivo Specificity of the Bcl11a Erythroid Enhancer","volume":"128","author":"Smith","year":"2016","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.omtm.2018.08.003","article-title":"Disruption of the BCL11A Erythroid Enhancer Reactivates Fetal Hemoglobin in Erythroid Cells of Patients with \u03b2-Thalassemia Major","volume":"10","author":"Psatha","year":"2018","journal-title":"Mol. Ther.-Methods Clin. Dev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.omtm.2016.12.009","article-title":"Long-Term Engraftment and Fetal Globin Induction upon BCL11A Gene Editing in Bone-Marrow-Derived CD34+ Hematopoietic Stem and Progenitor Cells","volume":"4","author":"Chang","year":"2017","journal-title":"Mol. Ther.-Methods Clin. Dev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1038\/nmeth.3554","article-title":"Functional Footprinting of Regulatory DNA","volume":"12","author":"Vierstra","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_12","unstructured":"(2021, March 21). Sangamo, Sanofi Show Positive Early Data for SCD Gene-Edited Cell Therapy. Available online: https:\/\/www.genengnews.com\/news\/sangamo-sanofi-show-positive-early-data-for-scd-gene-edited-cell-therapy\/."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1111\/bjh.17269","article-title":"Gene Therapy for Primary Immunodeficiencies","volume":"193","author":"Fox","year":"2021","journal-title":"Br. J. Haematol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/nature13420","article-title":"Targeted Genome Editing in Human Repopulating Haematopoietic Stem Cells","volume":"510","author":"Genovese","year":"2014","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"eaan0820","DOI":"10.1126\/scitranslmed.aan0820","article-title":"Preclinical Modeling Highlights the Therapeutic Potential of Hematopoietic Stem Cell Gene Editing for Correction of SCID-X1","volume":"9","author":"Schiroli","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1038\/s41467-019-09614-y","article-title":"Gene Correction for SCID-X1 in Long-Term Hematopoietic Stem Cells","volume":"10","author":"Wiebking","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e230","DOI":"10.1016\/S2352-3026(19)30066-3","article-title":"Gene Therapy for Wiskott-Aldrich Syndrome: Here to Stay","volume":"6","author":"Candotti","year":"2019","journal-title":"Lancet Haematol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.stemcr.2016.06.003","article-title":"Gene Correction of IPSCs from a Wiskott-Aldrich Syndrome Patient Normalizes the Lymphoid Developmental and Functional Defects","volume":"7","author":"Laskowski","year":"2016","journal-title":"Stem Cell Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2416","DOI":"10.1182\/blood-2015-09-672337","article-title":"Long-Term Multilineage Engraftment of Autologous Genome-Edited Hematopoietic Stem Cells in Nonhuman Primates","volume":"127","author":"Peterson","year":"2016","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/nrm3486","article-title":"TALENs: A Widely Applicable Technology for Targeted Genome Editing","volume":"14","author":"Joung","year":"2013","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"100007","DOI":"10.1016\/j.ggedit.2021.100007","article-title":"TALE and TALEN Genome Editing Technologies","volume":"2","author":"Becker","year":"2021","journal-title":"Gene Genome Ed."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/s43141-021-00225-z","article-title":"TALENs\u2014an Indispensable Tool in the Era of CRISPR: A Mini Review","volume":"19","author":"Bhardwaj","year":"2021","journal-title":"J. Genet. Eng. Biotechnol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41392-019-0089-y","article-title":"Applications of Genome Editing Technology in the Targeted Therapy of Human Diseases: Mechanisms, Advances and Prospects","volume":"5","author":"Li","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.omtm.2018.12.008","article-title":"TALEN-Mediated Gene Editing of HBG in Human Hematopoietic Stem Cells Leads to Therapeutic Fetal Hemoglobin Induction","volume":"12","author":"Lux","year":"2019","journal-title":"Mol. Ther.-Methods Clin. Dev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.omtm.2017.11.005","article-title":"A Nonhuman Primate Transplantation Model to Evaluate Hematopoietic Stem Cell Gene Editing Strategies for \u03b2-Hemoglobinopathies","volume":"8","author":"Humbert","year":"2018","journal-title":"Mol. Ther.-Methods Clin. Dev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"E497","DOI":"10.3324\/haematol.2018.215178","article-title":"Correction of IVS I-110(G>A) \u03b2-Thalassemia by CRISPR\/Cas- And TALEN-Mediated Disruption of Aberrant Regulatory Elements in Human Hematopoietic Stem and Progenitor Cells","volume":"104","author":"Patsali","year":"2019","journal-title":"Haematologica"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"srep12065","DOI":"10.1038\/srep12065","article-title":"Both TALENs and CRISPR\/Cas9 Directly Target the HBB IVS2-654 (C > T) Mutation in \u03b2-Thalassemiaderived IPSCs","volume":"5","author":"Xu","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e12491","DOI":"10.1111\/cpr.12491","article-title":"Treatment of \u0392654-Thalassaemia by TALENs in a Mouse Model","volume":"51","author":"Fang","year":"2018","journal-title":"Cell Prolif."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.stem.2015.02.005","article-title":"Lymphoid Regeneration from Gene-Corrected SCID-X1 Subject-Derived IPSCs","volume":"16","author":"Menon","year":"2015","journal-title":"Cell Stem Cell"},{"key":"ref_30","unstructured":"(2022, September 12). Cellectis Presents Initial Preclinical Data on Two Novel Gene Therapies for Patients with RAG1 Severe Combined Immunodeficiency (SCID) and Hyper IgE Syndrome at ESGCT 2021. Available online: https:\/\/cellectis.com\/en\/press\/cellectis-presents-initial-preclinical-data-on-two-novel-gene-therapies-for-patients-with-rag1-severe-combined-immunodeficiency-scid-and-hyper-ige-syndrome-at-esgct-2021."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1097\/QAI.0000000000001190","article-title":"TALEN-Mediated Knockout of CCR5 Confers Protection Against Infection of Human Immunodeficiency Virus","volume":"74","author":"Shi","year":"2017","journal-title":"JAIDS J. Acquir. Immune Defic. Syndr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e2000023","DOI":"10.1002\/biot.202000023","article-title":"Preclinical Evaluation of a Novel TALEN Targeting CCR5 Confirms Efficacy and Safety in Conferring Resistance to HIV-1 Infection","volume":"16","author":"Romito","year":"2021","journal-title":"Biotechnol. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1126\/science.1225829","article-title":"A Programmable Dual-RNA-Guided DNA Endonuclease in Adaptive Bacterial Immunity","volume":"337","author":"Jinek","year":"2012","journal-title":"Science"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1258096","DOI":"10.1126\/science.1258096","article-title":"The New Frontier of Genome Engineering with CRISPR-Cas9","volume":"346","author":"Doudna","year":"2014","journal-title":"Science"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1146\/annurev-biophys-062215-010822","article-title":"CRISPR\u2013Cas9 Structures and Mechanisms","volume":"46","author":"Jiang","year":"2017","journal-title":"Annu. Rev. Biophys."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1038\/nm.4170","article-title":"A Genome-Editing Strategy to Treat \u03b2-Hemoglobinopathies That Recapitulates a Mutation Associated with a Benign Genetic Condition","volume":"22","author":"Traxler","year":"2016","journal-title":"Nat. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3379","DOI":"10.1182\/bloodadvances.2019000820","article-title":"Genome Editing of HBG1 and HBG2 to Induce Fetal Hemoglobin","volume":"3","author":"Doerfler","year":"2019","journal-title":"Blood Adv."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1182\/blood-2017-10-811505","article-title":"Induction of Fetal Hemoglobin Synthesis by CRISPR\/Cas9-Mediated Editing of the Human b-Globin Locus","volume":"131","author":"Antoniani","year":"2018","journal-title":"Blood"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2945","DOI":"10.1182\/blood-2012-06-292078","article-title":"Reawakening Fetal Hemoglobin: Prospects for New Therapies for the \u03b2-Globin Disorders","volume":"120","author":"Bauer","year":"2012","journal-title":"Blood"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/s41588-021-00798-y","article-title":"Transcription Factor Competition at the \u03b3-Globin Promoters Controls Hemoglobin Switching","volume":"53","author":"Liu","year":"2021","journal-title":"Nat. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1126\/science.aad3312","article-title":"Gene Regulation: Transcription Factors LRF and BCL11A Independently Repress Expression of Fetal Hemoglobin","volume":"351","author":"Masuda","year":"2016","journal-title":"Science"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"10133","DOI":"10.1038\/s41598-020-66309-x","article-title":"Comparative Targeting Analysis of KLF1, BCL11A, and HBG1\/2 in CD34+ HSPCs by CRISPR\/Cas9 for the Induction of Fetal Hemoglobin","volume":"10","author":"Antony","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"6677","DOI":"10.1172\/JCI140189","article-title":"BCL11A Enhancer\u2013Edited Hematopoietic Stem Cells Persist in Rhesus Monkeys without Toxicity","volume":"130","author":"Demirci","year":"2020","journal-title":"J. Clin. Invest."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1182\/blood.2020010020","article-title":"Enhanced HbF Reactivation by Multiplex Mutagenesis of Thalassemic CD34+ Cells in Vitro and in Vivo","volume":"138","author":"Psatha","year":"2021","journal-title":"Blood"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1038\/s41591-019-0401-y","article-title":"Highly Efficient Therapeutic Gene Editing of Human Hematopoietic Stem Cells","volume":"25","author":"Wu","year":"2019","journal-title":"Nat. Med."},{"key":"ref_46","unstructured":"Locatelli, F., Frangoul, H., Corbacioglu, S., de la Fuente, J., Wall, D., Capellini, M.D., de Montalembert, M., Kattamis, A., Lobitz, S., and Rondelli, D. (2022, January 9\u201317). Efficacy and Safety of a Single Dose of Ctx001 For Transfusion-Dependent \u0392eta-Thalassemia And Severe Sickle Cell Disease. Proceedings of the Conference of European Hematology Association, Vienna, Austria."},{"key":"ref_47","unstructured":"(2022, June 20). ClinicalTrials.Gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/home."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.stem.2019.08.016","article-title":"NHEJ-Mediated Repair of CRISPR-Cas9-Induced DNA Breaks Efficiently Corrects Mutations in HSPCs from Patients with Fanconi Anemia","volume":"25","author":"Ugalde","year":"2019","journal-title":"Cell Stem Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4034","DOI":"10.1038\/s41467-020-17626-2","article-title":"Targeted Gene Correction of Human Hematopoietic Stem Cells for the Treatment of Wiskott-Aldrich Syndrome","volume":"11","author":"Rai","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"15577","DOI":"10.1038\/srep15577","article-title":"Genome Editing of CXCR4 by CRISPR\/Cas9 Confers Cells Resistant to HIV-1 Infection","volume":"5","author":"Hou","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1089\/hum.2017.032","article-title":"Simultaneous Knockout of CXCR4 and CCR5 Genes in CD4+ T Cells via CRISPR\/Cas9 Confers Resistance to Both X4- and R5-Tropic Human Immunodeficiency Virus Type 1 Infection","volume":"29","author":"Yu","year":"2018","journal-title":"Hum. Gene Ther."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1056\/NEJMoa1817426","article-title":"CRISPR-Edited Stem Cells in a Patient with HIV and Acute Lymphocytic Leukemia","volume":"381","author":"Xu","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1038\/s41591-018-0049-z","article-title":"CRISPR-Cas9 Genome Editing Induces a P53-Mediated DNA Damage Response","volume":"24","author":"Haapaniemi","year":"2018","journal-title":"Nat. Med."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Mirgayazova, R., Khadiullina, R., Chasov, V., Mingaleeva, R., Miftakhova, R., Rizvanov, A., and Bulatov, E. (2020). Therapeutic Editing of the TP53 Gene: Is Crispr\/CAS9 an Option?. Genes, 11.","DOI":"10.3390\/genes11060704"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.stem.2019.02.019","article-title":"Precise Gene Editing Preserves Hematopoietic Stem Cell Function Following Transient P53-Mediated DNA Damage Response","volume":"24","author":"Schiroli","year":"2019","journal-title":"Cell Stem Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1038\/s41588-021-00838-7","article-title":"Chromothripsis as an On-Target Consequence of CRISPR\u2013Cas9 Genome Editing","volume":"53","author":"Leibowitz","year":"2021","journal-title":"Nat. Genet."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1038\/s41467-019-09006-2","article-title":"CRISPR-Cas9 Genome Editing Induces Megabase-Scale Chromosomal Truncations","volume":"10","author":"Cullot","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1016\/j.cell.2020.10.025","article-title":"Allele-Specific Chromosome Removal after Cas9 Cleavage in Human Embryos","volume":"183","author":"Zuccaro","year":"2020","journal-title":"Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cell.2010.11.055","article-title":"Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development","volume":"144","author":"Stephens","year":"2011","journal-title":"Cell"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1146\/annurev-biochem-013118-111730","article-title":"Evaluating and Enhancing Target Specificity of Gene-Editing Nucleases and Deaminases","volume":"88","author":"Kim","year":"2019","journal-title":"Annu. Rev. Biochem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"649896","DOI":"10.3389\/fmed.2021.649896","article-title":"CRISPR\/Cas: Advances, Limitations, and Applications for Precision Cancer Research","volume":"8","author":"Yang","year":"2021","journal-title":"Front. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/s41586-019-1711-4","article-title":"Search-and-Replace Genome Editing without Double-Strand Breaks or Donor DNA","volume":"576","author":"Anzalone","year":"2019","journal-title":"Nature"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/s41573-020-0084-6","article-title":"Base Editing: Advances and Therapeutic Opportunities","volume":"19","author":"Porto","year":"2020","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1038\/nature24644","article-title":"Programmable Base Editing of T to G C in Genomic DNA without DNA Cleavage","volume":"551","author":"Gaudelli","year":"2017","journal-title":"Nature"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/nature17946","article-title":"Programmable Editing of a Target Base in Genomic DNA without Double-Stranded DNA Cleavage","volume":"533","author":"Komor","year":"2016","journal-title":"Nature"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1126\/science.aas9129","article-title":"Engineered CRISPR-Cas9 Nuclease with Expanded Targeting Space","volume":"9","author":"Nishimasu","year":"2018","journal-title":"Science"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Kantor, A., and Mcclements, M.E. (2020). CRISPR-Cas9 DNA Base-Editing and Prime-Editing. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176240"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1038\/s41587-020-0491-6","article-title":"Directed Evolution of Adenine Base Editors with Increased Activity and Therapeutic Application","volume":"38","author":"Gaudelli","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/s41591-020-0790-y","article-title":"Therapeutic Base Editing of Human Hematopoietic Stem Cells","volume":"26","author":"Zeng","year":"2020","journal-title":"Nat. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/s41422-019-0267-z","article-title":"Reactivation of \u03b3-Globin Expression through Cas9 or Base Editor to Treat \u03b2-Hemoglobinopathies","volume":"30","author":"Wang","year":"2020","journal-title":"Cell Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"6618","DOI":"10.1038\/s41467-022-34493-1","article-title":"Base-Editing-Mediated Dissection of a \u03b3 -Globin Cis -Regulatory Element for the Therapeutic Reactivation of Fetal Hemoglobin Expression","volume":"13","author":"Antoniou","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/s41586-021-03609-w","article-title":"Base Editing of Haematopoietic Stem Cells Rescues Sickle Cell Disease in Mice","volume":"595","author":"Newby","year":"2021","journal-title":"Nature"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1182\/bloodadvances.2020003702","article-title":"In Vivo HSPC Gene Therapy with Base Editors Allows for Efficient Reactivation of Fetal G-Globin in b-YAC Mice","volume":"5","author":"Li","year":"2021","journal-title":"Blood Adv."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"577053","DOI":"10.3389\/fgene.2020.577053","article-title":"Transcriptome Analyses of \u03b2-Thalassemia \u221228(A>G) Mutation Using Isogenic Cell Models Generated by CRISPR\/Cas9 and Asymmetric Single-Stranded Oligodeoxynucleotides (AssODNs)","volume":"11","author":"Li","year":"2020","journal-title":"Front. Genet."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1038\/nbt.4199","article-title":"An Apobec3a-Cas9 Base Editor with Minimized Bystander and off-Target Activities","volume":"36","author":"Gehrke","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.ymthe.2021.10.026","article-title":"Disruption of HIV-1 Co-Receptors CCR5 and CXCR4 in Primary Human T Cells and Hematopoietic Stem and Progenitor Cells Using Base Editing","volume":"30","author":"Knipping","year":"2022","journal-title":"Mol. Ther."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Siegner, S.M., Clemens, A., Ugalde, L., Garcia-Garcia, L., Bueren, J.A., Rio, P., Karasu, M.E., and Corn, J.E. (2022). Adenine Base Editing Is an Efficient Approach to Restore Function in FA Patient Cells without Double-Stranded DNA Breaks. bioRxiv, 2022.04.22.489197.","DOI":"10.1101\/2022.04.22.489197"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"McAuley, G.E., Yiu, G., Newby, G.A., Kang, S.H.L., Garibay, A.J., Butler, J.A., Christian, V.S., Fitz-Gibbon, S., Wong, R.L., and Everette, K.A. (2022, January 16\u201319). Base Editing of Hematopoietic Stem Cells Rescues T-Cell Development for CD3d Severe Combined Immunodeficiency. Proceedings of the American Society of Gene and Cell Therapy, Annual Meeting, Washington, DC, USA.","DOI":"10.1182\/blood-2022-170634"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"5352","DOI":"10.1038\/s41467-020-19136-7","article-title":"Prime Editing for Functional Repair in Patient-Derived Disease Models","volume":"11","author":"Schene","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1038\/s41587-020-0561-9","article-title":"Genome Editing with CRISPR\u2013Cas Nucleases, Base Editors, Transposases and Prime Editors","volume":"38","author":"Anzalone","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"5635","DOI":"10.1016\/j.cell.2021.09.018","article-title":"Enhanced Prime Editing Systems by Manipulating Cellular Determinants of Editing Outcomes","volume":"184","author":"Chen","year":"2021","journal-title":"Cell"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/nature05913","article-title":"Perceptions of Epigenetics","volume":"447","author":"Bird","year":"2007","journal-title":"Nature"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.semcdb.2020.07.002","article-title":"Control of the Chromatin Response to DNA Damage: Histone Proteins Pull the Strings","volume":"113","author":"Ferrand","year":"2021","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1101\/gad.276568.115","article-title":"Role of TET Enzymes in DNA Methylation, Development, and Cancer","volume":"30","author":"Rasmussen","year":"2016","journal-title":"Genes Dev."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Milazzo, G., Mercatelli, D., Di Muzio, G., Triboli, L., De Rosa, P., Perini, G., and Giorgi, F.M. (2020). Histone Deacetylases (HDACs): Evolution, Specificity, Role in Transcriptional Complexes, and Pharmacological Actionability. Genes, 11.","DOI":"10.3390\/genes11050556"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/978-981-15-8104-5_4","article-title":"Histone Mutations and Bone Cancers","volume":"1283","author":"Taylor","year":"2021","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Syding, L.A., Nickl, P., Kasparek, P., and Sedlacek, R. (2020). CRISPR\/Cas9 Epigenome Editing Potential for Rare Imprinting Diseases: A Review. Cells, 9.","DOI":"10.3390\/cells9040993"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"350","DOI":"10.4161\/epi.19507","article-title":"Epigenetic Reprogramming of Cancer Cells via Targeted DNA Methylation","volume":"7","author":"Rivenbark","year":"2012","journal-title":"Epigenetics."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1172\/JCI77321","article-title":"TALE-Mediated Epigenetic Suppression of CDKN2A Increases Replication in Human Fibroblasts","volume":"125","author":"Bernstein","year":"2015","journal-title":"J. Clin. Invest."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1186\/s13059-017-1306-z","article-title":"DNA Epigenome Editing Using CRISPR-Cas SunTag-Directed DNMT3A","volume":"18","author":"Huang","year":"2017","journal-title":"Genome Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"16009","DOI":"10.1038\/celldisc.2016.9","article-title":"A CRISPR-Based Approach for Targeted DNA Demethylation","volume":"2","author":"Xu","year":"2016","journal-title":"Cell Discov."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.cell.2016.09.006","article-title":"Inheritable Silencing of Endogenous Genes by Hit-and-Run Targeted Epigenetic Editing","volume":"167","author":"Amabile","year":"2016","journal-title":"Cell"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1016\/j.cell.2017.10.025","article-title":"In Vivo Target Gene Activation via CRISPR\/Cas9-Mediated Trans-Epigenetic Modulation","volume":"171","author":"Liao","year":"2017","journal-title":"Cell"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1818","DOI":"10.1016\/j.ymthe.2018.04.017","article-title":"In Situ Gene Therapy via AAV-CRISPR-Cas9-Mediated Targeted Gene Regulation","volume":"26","author":"Moreno","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2503","DOI":"10.1016\/j.cell.2021.03.025","article-title":"Genome-Wide Programmable Transcriptional Memory by CRISPR-Based Epigenome Editing","volume":"184","author":"Chen","year":"2021","journal-title":"Cell"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/s41592-021-01124-4","article-title":"Programmable RNA Editing with Compact CRISPR\u2013Cas13 Systems from Uncultivated Microbes","volume":"18","author":"Xu","year":"2021","journal-title":"Nat. Methods"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"aaf5573","DOI":"10.1126\/science.aaf5573","article-title":"C2c2 Is a Single-Component Programmable RNA-Guided RNA-Targeting CRISPR Effector","volume":"353","author":"Abudayyeh","year":"2016","journal-title":"Science"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1038\/nature24049","article-title":"RNA Targeting with CRISPR-Cas13","volume":"550","author":"Abudayyeh","year":"2017","journal-title":"Nature"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1126\/science.aaq0180","article-title":"RNA Editing with CRISPR-Cas13","volume":"358","author":"Cox","year":"2017","journal-title":"Science"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"677587","DOI":"10.3389\/fcell.2021.677587","article-title":"Programmable System of Cas13-Mediated RNA Modification and Its Biological and Biomedical Applications","volume":"9","author":"Tang","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"41478","DOI":"10.1038\/srep41478","article-title":"Construction of a Guide-RNA for Site-Directed RNA Mutagenesis Utilising Intracellular A-To-I RNA Editing","volume":"7","author":"Fukuda","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1016\/j.molcel.2019.09.013","article-title":"Programmable Inhibition and Detection of RNA Viruses Using Cas13","volume":"76","author":"Freije","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/j.cell.2020.04.020","article-title":"Development of CRISPR as an Antiviral Strategy to Combat SARS-CoV-2 and Influenza","volume":"181","author":"Abbott","year":"2020","journal-title":"Cell"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.omtn.2020.05.030","article-title":"CRISPR-Cas13a Inhibits HIV-1 Infection","volume":"21","author":"Yin","year":"2020","journal-title":"Mol. Ther.-Nucleic Acids"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2855","DOI":"10.1182\/blood-2007-04-082602","article-title":"Hematopoietic Stem-Cell Gene Therapy of Hemophilia A Incorporating a Porcine Factor VIII Transgene and Nonmyeloablative Conditioning Regimens","volume":"110","author":"Ide","year":"2007","journal-title":"Blood"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/S0958-1669(98)80029-3","article-title":"Lentiviruses as Gene Transfer Agents for Delivery to Non-Dividing Cells","volume":"9","author":"Naldini","year":"1998","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S0092-8674(02)00864-4","article-title":"HIV-1 Integration in the Human Genome Favors Active Genes and Local Hotspots","volume":"110","author":"Shinn","year":"2002","journal-title":"Cell"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1233151","DOI":"10.1126\/science.1233151","article-title":"Lentiviral Hematopoietic Stem Cell Gene Therapy in Patients with Wiskott-Aldrich Syndrome","volume":"341","author":"Aiuti","year":"2013","journal-title":"Science"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"e239","DOI":"10.1016\/S2352-3026(19)30021-3","article-title":"Lentiviral Haemopoietic Stem\/Progenitor Cell Gene Therapy for Treatment of Wiskott-Aldrich Syndrome: Interim Results of a Non-Randomised, Open-Label, Phase 1\/2 Clinical Study","volume":"6","author":"Ferrua","year":"2019","journal-title":"Lancet Haematol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1056\/NEJMoa1815408","article-title":"Lentiviral Gene Therapy Combined with Low-Dose Busulfan in Infants with SCID-X1","volume":"380","author":"Mamcarz","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1056\/NEJMoa2027675","article-title":"Autologous Ex Vivo Lentiviral Gene Therapy for Adenosine Deaminase Deficiency","volume":"384","author":"Kohn","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1056\/NEJMoa1705342","article-title":"Gene Therapy in Patients with Transfusion-Dependent \u03b2-Thalassemia","volume":"378","author":"Thompson","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1233158","DOI":"10.1126\/science.1233158","article-title":"Lentiviral Hematopoietic Stem Cell Gene Therapy Benefits Metachromatic Leukodystrophy","volume":"341","author":"Biffi","year":"2013","journal-title":"Science"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/B978-0-12-386509-0.00010-7","article-title":"Lentiviral Hematopoietic Cell Gene Therapy for X-Linked Adrenoleukodystrophy","volume":"507","author":"Cartier","year":"2012","journal-title":"Methods Enzymol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1126\/science.272.5259.263","article-title":"In Vivo Gene Delivery and Stable Transduction of Nondividing Cells by a Lentiviral Vector","volume":"272","author":"Naldini","year":"1996","journal-title":"Science"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.trsl.2012.12.018","article-title":"Immune Responses in Liver-Directed Lentiviral Gene Therapy","volume":"161","author":"Annoni","year":"2013","journal-title":"Transl. Res."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.15252\/emmm.201708148","article-title":"Genome Editing for Scalable Production of Alloantigen-free Lentiviral Vectors for in Vivo Gene Therapy","volume":"9","author":"Milani","year":"2017","journal-title":"EMBO Mol. Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"6708","DOI":"10.1128\/JVI.73.8.6708-6714.1999","article-title":"The Resistance of Retroviral Vectors Produced from Human Cells to Serum Inactivation In Vivo and In Vitro Is Primate Species Dependent","volume":"73","author":"DePolo","year":"1999","journal-title":"J. Virol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1182\/blood-2014-02-558163","article-title":"Baboon Envelope Pseudotyped LVs Outperform VSV-G-LVs for Gene Transfer into Early-Cytokine-Stimulated and Resting HSCs","volume":"124","author":"Amirache","year":"2014","journal-title":"Blood"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1038\/gt.2013.1","article-title":"Engineering a Serum-Resistant and Thermostable Vesicular Stomatitis Virus G Glycoprotein for Pseudotyping Retroviral and Lentiviral Vectors","volume":"20","author":"Hwang","year":"2013","journal-title":"Gene Ther."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1089\/hum.2020.127","article-title":"In Vivo Gene Therapy for Canine SCID-X1 Using Cocal-Pseudotyped Lentiviral Vector","volume":"32","author":"Rajawat","year":"2021","journal-title":"Hum. Gene Ther."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2873","DOI":"10.3389\/fimmu.2019.02873","article-title":"Efficient and Robust NK-Cell Transduction With Baboon Envelope Pseudotyped Lentivector","volume":"10","author":"Colamartino","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Gutierrez-Guerrero, A., Cosset, F.L., and Verhoeyen, E. (2020). Lentiviral Vector Pseudotypes: Precious Tools to Improve Gene Modification of Hematopoietic Cells for Research and Gene Therapy. Viruses, 12.","DOI":"10.3390\/v12091016"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"3578","DOI":"10.1182\/blood-2013-11-538926","article-title":"Intravenous Injection of a Foamy Virus Vector to Correct Canine SCID-X1","volume":"123","author":"Burtner","year":"2014","journal-title":"Blood"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1182\/bloodadvances.2017007773","article-title":"Measles Virus Envelope Pseudotyped Lentiviral Vectors Transduce Quiescent Human HSCs at an Efficiency without Precedent","volume":"1","author":"Amirache","year":"2017","journal-title":"Blood Adv."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.omtm.2017.04.002","article-title":"Integrase-Deficient Lentiviral Vector as an All-in-One Platform for Highly Efficient CRISPR\/Cas9-Mediated Gene Editing","volume":"5","author":"Ortinski","year":"2017","journal-title":"Mol. Ther.-Methods Clin. Dev."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.omtm.2018.02.009","article-title":"A Non-Integrating Lentiviral Approach Overcomes Cas9-Induced Immune Rejection to Establish an Immunocompetent Metastatic Renal Cancer Model","volume":"9","author":"Hu","year":"2018","journal-title":"Mol. Ther.-Methods Clin. Dev."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"6409","DOI":"10.1038\/srep06409","article-title":"Novel Lentiviral Vectors with Mutated Reverse Transcriptase for MRNA Delivery of TALE Nucleases","volume":"4","author":"Mock","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_129","first-page":"681","article-title":"Alipogene Tiparvovec, an Adeno-Associated Virus Encoding the Ser(447)X Variant of the Human Lipoprotein Lipase Gene for the Treatment of Patients with Lipoprotein Lipase Deficiency","volume":"11","year":"2009","journal-title":"Curr. Opin. Mol. Ther."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/S0140-6736(17)31868-8","article-title":"Efficacy and Safety of Voretigene Neparvovec (AAV2-HRPE65v2) in Patients with RPE65-Mediated Inherited Retinal Dystrophy: A Randomised, Controlled, Open-Label, Phase 3 Trial","volume":"390","author":"Russell","year":"2017","journal-title":"Lancet"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1007\/s40265-019-01162-5","article-title":"Onasemnogene Abeparvovec: First Global Approval","volume":"79","author":"Hoy","year":"2019","journal-title":"Drugs"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"5656","DOI":"10.1128\/jvi.68.9.5656-5666.1994","article-title":"Efficient Gene Transfer into Nondividing Cells by Adeno-Associated Virus-Based Vectors","volume":"68","author":"Podsakoff","year":"1994","journal-title":"J. Virol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.ymthe.2020.01.001","article-title":"Immune Responses to Viral Gene Therapy Vectors","volume":"28","author":"Shirley","year":"2020","journal-title":"Mol. Ther."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/sj.gt.3301068","article-title":"Efficient Gene Transfer into Human Cord Blood CD34+ Cells and the CD34+CD38- Subset Using Highly Purified Recombinant Adeno-Associated Viral Vector Preparations That Are Free of Helper Virus and Wild-Type AAV","volume":"7","author":"Nathwani","year":"2000","journal-title":"Gene Ther."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"11053","DOI":"10.1073\/pnas.0502902102","article-title":"Recombinant AAV2 Transduction of Primitive Human Hematopoietic Stem Cells Capable of Serial Engraftment in Immune-Deficient Mice","volume":"102","author":"Santat","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1084\/jem.179.6.1867","article-title":"Adeno-Associated Virus 2-Mediated High Efficiency Gene Transfer into Irm, Nature and Mature Subsets of Hematopoietic Progenitor Cells in Human Umbilical Cord Blood","volume":"179","author":"Zhou","year":"1994","journal-title":"J. Exp. Med."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"8262","DOI":"10.1128\/jvi.71.11.8262-8267.1997","article-title":"Adeno-Associated Virus Type 2-Mediated Transduction in Primary Human Bone Marrow-Derived CD34+ Hematopoietic Progenitor Cells: Donor Variation and Correlation of Transgene Expression with Cellular Differentiation","volume":"71","author":"Ponnazhagan","year":"1997","journal-title":"J. Virol."},{"key":"ref_138","first-page":"2167","article-title":"High-Level Globin Gene Expression Mediated by a Recombinant Adeno- Associated Virus Genome That Contains the 3* g Globin Gene Regulatory Element and Integrates as Tandem Copies in Erythroid Cells","volume":"89","author":"Hargrove","year":"1997","journal-title":"Red Cells"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1128\/jvi.71.3.1776-1783.1997","article-title":"Recombinant Adeno-Associated Virus Mediates a High Level of Gene Transfer but Less Efficient Integration in the K562 Human Hematopoietic Cell Line","volume":"71","author":"Malik","year":"1997","journal-title":"J. Virol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/j.jcyt.2013.04.003","article-title":"Optimizing the Transduction Efficiency of Human Hematopoietic Stem Cells Using Capsid-Modified AAV6 Vectors in Vitro and in a Xenograft Mouse Model in Vivo","volume":"15","author":"Song","year":"2014","journal-title":"Cytotherapy"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.omtn.2019.05.025","article-title":"In Vivo Outcome of Homology-Directed Repair at the HBB Gene in HSC Using Alternative Donor Template Delivery Methods","volume":"17","author":"Pattabhi","year":"2019","journal-title":"Mol. Ther.-Nucleic Acids"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1038\/s41467-021-20909-x","article-title":"Cas9-AAV6 Gene Correction of \u03b2-Globin in Autologous HSCs Improves Sickle Cell Disease Erythropoiesis in Mice","volume":"12","author":"Wilkinson","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1016\/j.ymthe.2019.05.014","article-title":"Editing the Sickle Cell Disease Mutation in Human Hematopoietic Stem Cells: Comparison of Endonucleases and Homologous Donor Templates","volume":"27","author":"Romero","year":"2019","journal-title":"Mol. Ther."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1038\/nbt.3408","article-title":"Homology-Driven Genome Editing in Hematopoietic Stem and Progenitor Cells Using Zinc Finger Nuclease MRNA and AAV6 Donors","volume":"33","author":"Wang","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/j.stem.2019.04.001","article-title":"Highly Efficient and Marker-Free Genome Editing of Human Pluripotent Stem Cells by CRISPR-Cas9 RNP and AAV6 Donor-Mediated Homologous Recombination","volume":"24","author":"Martin","year":"2019","journal-title":"Cell Stem Cell"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1743-422X-10-74","article-title":"A Survey of Ex Vivo\/in Vitro Transduction Efficiency of Mammalian Primary Cells and Cell Lines with Nine Natural Adeno-Associated Virus (AAV1-9) and One Engineered Adeno-Associated Virus Serotype","volume":"10","author":"Ellis","year":"2013","journal-title":"Virol. J."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/nature10177","article-title":"In Vivo Genome Editing Restores Hemostasis in a Mouse Model of Hemophilia","volume":"475","author":"Li","year":"2012","journal-title":"Nature"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.cell.2018.02.033","article-title":"Transcriptome Engineering with RNA-Targeting Type VI-D CRISPR Effectors","volume":"173","author":"Konermann","year":"2018","journal-title":"Cell"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.molcel.2018.02.028","article-title":"Cas13d Is a Compact RNA-Targeting Type VI CRISPR Effector Positively Modulated by a WYL-Domain-Containing Accessory Protein","volume":"70","author":"Yan","year":"2018","journal-title":"Mol. Cell"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"100764","DOI":"10.1016\/j.isci.2019.100764","article-title":"Ex Vivo\/In Vivo Gene Editing in Hepatocytes Using \u201cAll-in-One\u201d CRISPR-Adeno-Associated Virus Vectors with a Self-Linearizing Repair Template","volume":"23","author":"Krooss","year":"2020","journal-title":"iScience"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1038\/s41467-018-04048-4","article-title":"RNA-Guided Transcriptional Silencing in Vivo with S. Aureus CRISPR-Cas9 Repressors","volume":"9","author":"Thakore","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/nature14299","article-title":"In Vivo Genome Editing Using Staphylococcus Aureus Cas9","volume":"520","author":"Ran","year":"2015","journal-title":"Nature"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1128\/CVI.05107-11","article-title":"Adeno-Associated Virus Antibody Profiles in Newborns, Children, and Adolescents","volume":"18","author":"Calcedo","year":"2011","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/mt.2011.177","article-title":"Neutralizing Antibodies against AAV Serotypes 1, 2, 6, and 9 in Sera of Commonly Used Animal Models","volume":"20","author":"Rapti","year":"2012","journal-title":"Mol. Ther."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"2963","DOI":"10.1182\/blood-2002-10-3296","article-title":"AAV-Mediated Factor IX Gene Transfer to Skeletal Muscle in Patients with Severe Hemophilia B","volume":"101","author":"Manno","year":"2003","journal-title":"Blood"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"S45","DOI":"10.1126\/scitranslmed.3005795","article-title":"Overcoming Pre-Existing Humoral Immunity to AAV Using Capsid Decoys","volume":"5","author":"Mingozzi","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/gt.2015.109","article-title":"Prevalence of AAV1 Neutralizing Antibodies and Consequences for a Clinical Trial of Gene Transfer for Advanced Heart Failure","volume":"23","author":"Greenberg","year":"2016","journal-title":"Gene Ther."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.omtm.2019.05.009","article-title":"Therapeutic HFIX Activity Achieved after Single AAV5-HFIX Treatment in Hemophilia B Patients and NHPs with Pre-Existing Anti-AAV5 NABs","volume":"14","author":"Majowicz","year":"2019","journal-title":"Mol. Ther.-Methods Clin. Dev."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1089\/hum.2020.182","article-title":"Moving Forward after Two Deaths in a Gene Therapy Trial of Myotubular Myopathy","volume":"31","author":"Wilson","year":"2020","journal-title":"Hum. Gene Ther."},{"key":"ref_160","unstructured":"Taylor, P. (2022, September 12). Astellas Reports Fourth Death in Halted Gene Therapy Trial. Available online: https:\/\/www.medscape.com\/viewarticle\/979152."},{"key":"ref_161","unstructured":"Burton, K.W. (2022, September 12). Two Deaths From Liver Failure Linked to Spinal Muscular Atrophy Drug. Available online: https:\/\/pharmaphorum.com\/news\/astellas-reports-fourth-death-in-halted-gene-therapy-trial\/."},{"key":"ref_162","first-page":"84","article-title":"Isolation of a Cytopathogenic Agent from Human Adenoids LTndergoing Spontaneous Degeneration in Tissue Culture","volume":"64","author":"Rowe","year":"1952","journal-title":"World Health Organ. Monogr. Ser."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1126\/science.2017680","article-title":"Adenovirus-Mediated Transfer of a Recombinant A1-Antitrypsin Gene to the Lung Epithelium in Vivo","volume":"252","author":"Rosenfeld","year":"1991","journal-title":"Science"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"6729","DOI":"10.1128\/JVI.73.8.6729-6742.1999","article-title":"Variability of Human Systemic Humoral Immune Responses to Adenovirus Gene Transfer Vectors Administered to Different Organs","volume":"73","author":"Harvey","year":"1999","journal-title":"J. Virol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1089\/hum.2013.2527","article-title":"Adenovirus: The First Effective in Vivo Gene Delivery Vector","volume":"25","author":"Crystal","year":"2014","journal-title":"Hum. Gene Ther."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.ymgme.2003.08.016","article-title":"Fatal Systemic Inflammatory Response Syndrome in a Ornithine Transcarbamylase Deficient Patient Following Adenoviral Gene Transfer","volume":"80","author":"Raper","year":"2003","journal-title":"Mol. Genet. Metab."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1089\/hum.1995.6.8-1039","article-title":"Gene Therpy for Hemophilia B: Host Prolongs the Therapeutic Effect o f Factor I X Immunosuppression","volume":"1044","author":"Fang","year":"1995","journal-title":"Hum. Gene Ther."},{"key":"ref_168","first-page":"496","article-title":"Transient Immunosuppression Permits Successful Repetitive Intravenous Administration of an Adenovirus Vector","volume":"3","author":"White","year":"1996","journal-title":"Gene Ther."},{"key":"ref_169","first-page":"1391","article-title":"Immunosuppression to Control the Immune Reactions Triggered by First-Generation Gene Transfer","volume":"1401","author":"Goulet","year":"1995","journal-title":"Hum. Gene Ther."},{"key":"ref_170","first-page":"521","article-title":"Brackmann\u2019 Stabilization of Transgene Expression by Incorporation of E3 Region Genes into an Adenoviral Factor IX Vector and by Transient Anti-CD4 Treatment of the Host","volume":"3","author":"Poller","year":"1996","journal-title":"Gene Ther."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1089\/hum.1996.7.4-499","article-title":"Anti-T Cell Receptor Monoclonal Antibody Transgene Expression Following Gene Prolongs Vivo Adenovirus-Mediated In Synovium Transfer to Mouse Synovium","volume":"7","author":"Sawchuk","year":"1996","journal-title":"Hum Gene Ther."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0022-5223(99)70462-9","article-title":"Transgene Expression after Adenovirus-Mediated Retransfection of Rat Lungs Is Increased and Prolonged by Transplant Immunosuppression","volume":"117","author":"Cassivi","year":"1999","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"6390","DOI":"10.1128\/JVI.00514-11","article-title":"Multimerization of Adenovirus Serotype 3 Fiber Knob Domains Is Required for Efficient Binding of Virus to Desmoglein 2 and Subsequent Opening of Epithelial Junctions","volume":"85","author":"Wang","year":"2011","journal-title":"J. Virol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1038\/nm952","article-title":"CD46 Is a Cellular Receptor for Group B Adenoviruses","volume":"9","author":"Gaggar","year":"2003","journal-title":"Nat. Med."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.ymthe.2003.12.014","article-title":"Functionally Distinct Subpopulations of Cord Blood CD34+ Cells Are Transduced by Adenoviral Vectors with Serotype 5 or 35 Tropism","volume":"9","author":"Nilsson","year":"2004","journal-title":"Mol. Ther."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"2567","DOI":"10.1128\/JVI.74.6.2567-2583.2000","article-title":"Efficient Gene Transfer into Human CD34+ Cells by a Retargeted Adenovirus Vector","volume":"74","author":"Shayakhmetov","year":"2000","journal-title":"J. Virol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1089\/hum.2005.16.664","article-title":"Evaluation of Biodistribution and Safety of Adenovirus Vectors Containing Group B Fibers after Intravenous Injection into Baboons","volume":"16","author":"Ni","year":"2005","journal-title":"Hum. Gene Ther."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"S18","DOI":"10.1038\/sj.gt.3302612","article-title":"Gutless Adenovirus: Last-Generation Adenovirus for Gene Therapy","volume":"12","author":"Alba","year":"2005","journal-title":"Gene Ther."},{"key":"ref_179","doi-asserted-by":"crossref","unstructured":"Ricobaraza, A., Gonzalez-Aparicio, M., Mora-Jimenez, L., Lumbreras, S., and Hernandez-Alcoceba, R. (2020). High-Capacity Adenoviral Vectors: Expanding the Scope of Gene Therapy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21103643"},{"key":"ref_180","doi-asserted-by":"crossref","unstructured":"Sandoval-Villegas, N., Nurieva, W., Amberger, M., and Ivics, Z. (2021). Contemporary Transposon Tools: A Review and Guide through Mechanisms and Applications of Sleeping Beauty, Piggybac and Tol2 for Genome Engineering. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22105084"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1089\/hum.2014.123","article-title":"A Hybrid Adenoviral Vector System Achieves Efficient Long-Term Gene Expression in the Liver via PiggyBac Transposition","volume":"26","author":"Smith","year":"2015","journal-title":"Hum. Gene Ther."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"2206","DOI":"10.1182\/blood-2016-04-711580","article-title":"In Vivo Transduction of Primitive Mobilized Hematopoietic Stem Cells after Intravenous Injection of Integrating Adenovirus Vectors","volume":"128","author":"Richter","year":"2016","journal-title":"Blood"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.omtm.2017.11.004","article-title":"A Combined in Vivo HSC Transduction\/Selection Approach Results in Efficient and Stable Gene Expression in Peripheral Blood Cells in Mice","volume":"8","author":"Wang","year":"2018","journal-title":"Mol. Ther.-Methods Clin. Dev."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1089\/hgtb.2014.005","article-title":"Superior Long-Term Repopulating Capacity of G-CSF + Plerixafor-Mobilized Blood: Implications for Stem Cell Gene Therapy by Studies in the Hbbth-3 Mouse Model","volume":"25","author":"Psatha","year":"2014","journal-title":"Hum. Gene Ther. Methods"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1089\/hum.2013.163","article-title":"Hematopoietic Stem Cell Mobilization for Gene Therapy: Superior Mobilization by the Combination of Granulocyte-Colony Stimulating Factor plus Plerixafor in Patients with \u03b2-Thalassemia Major","volume":"24","author":"Yannaki","year":"2013","journal-title":"Hum. Gene Ther."},{"key":"ref_186","first-page":"447","article-title":"The Combination of AMD3100+G-CSF Successfully Mobilizes HSCs into the Peripheral Blood Compared to G-CSF Alone, in a Thalassemic Mouse Model","volume":"95","author":"Psatha","year":"2010","journal-title":"Haematol. Hematol. J."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1182\/blood-2015-03-629618","article-title":"Plerixafor+G-CSF-Mobilized CD34+ Cells Represent an Optimal Graft Source for Thalassemia Gene Therapy","volume":"126","author":"Karponi","year":"2015","journal-title":"Blood"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1111\/trf.16721","article-title":"A New Step in Understanding Stem Cell Mobilization in Patients with Fanconi Anemia: A Bridge to Gene Therapy","volume":"62","author":"Diana","year":"2021","journal-title":"Transfussion"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"749","DOI":"10.3324\/haematol.2018.190876","article-title":"Hematopoietic Stem Cell Mobilization with Plerixafor in Sickle Cell Disease","volume":"103","author":"Hsieh","year":"2018","journal-title":"Haematologica"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"e497","DOI":"10.3324\/haematol.2019.236182","article-title":"Safe and Efficient Peripheral Blood Stem Cell Collection in Patients with Sickle Cell Disease Using Plerixafor","volume":"105","author":"Uchida","year":"2020","journal-title":"Hematologica"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"2883","DOI":"10.1182\/bloodadvances.2019000706","article-title":"High-Level Protein Production in Erythroid Cells Derived from in Vivo Transduced Hematopoietic Stem Cells","volume":"3","author":"Wang","year":"2019","journal-title":"Blood Adv."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1182\/bloodadvances.2018016451","article-title":"Rapid Immune Reconstitution of SCID-X1 Canines after G-CSF\/AMD3100 Mobilization and in Vivo Gene Therapy","volume":"2","author":"Humbert","year":"2018","journal-title":"Blood Adv."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.omtm.2018.02.004","article-title":"Integrating HDAd5\/35++ Vectors as a New Platform for HSC Gene Therapy of Hemoglobinopathies","volume":"9","author":"Li","year":"2018","journal-title":"Mol. Ther.-Methods Clin. Dev."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1172\/JCI122836","article-title":"In Vivo Hematopoietic Stem Cell Gene Therapy Ameliorates Murine Thalassemia Intermedia","volume":"129","author":"Wang","year":"2019","journal-title":"J. Clin. Invest."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"e139538","DOI":"10.1172\/jci.insight.139538","article-title":"Curative in Vivo Hematopoietic Stem Cell Gene Therapy of Murine Thalassemia Using Large Regulatory Elements","volume":"5","author":"Wang","year":"2020","journal-title":"JCI Insight"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"587269","DOI":"10.3389\/fcimb.2020.587269","article-title":"SARS-CoV-2: Structure, Biology, and Structure-Based Therapeutics Development","volume":"10","author":"Wang","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1089\/hum.2021.295","article-title":"In Vivo Hematopoietic Stem Cell Gene Therapy for SARS-CoV2 Infection Using a Decoy Receptor","volume":"33","author":"Wang","year":"2022","journal-title":"Hum. Gene Ther."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"14057","DOI":"10.1038\/mtm.2014.57","article-title":"Efficient Genome Editing in Hematopoietic Stem Cells with Helper-Dependent Ad5\/35 Vectors Expressing Site-Specific Endonucleases under MicroRNA Regulation","volume":"2","author":"Saydaminova","year":"2015","journal-title":"Mol. Ther.-Methods Clin. Dev."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"2915","DOI":"10.1182\/blood-2018-03-838540","article-title":"Reactivation of G-Globin in Adult b-YAC Mice after Ex Vivo and in Vivo Hematopoietic Stem Cell Genome Editing","volume":"131","author":"Li","year":"2018","journal-title":"Blood"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1016\/j.ymthe.2019.08.006","article-title":"Targeted Integration and High-Level Transgene Expression in AAVS1 Transgenic Mice after In Vivo HSC Transduction with HDAd5\/35++ Vectors","volume":"27","author":"Li","year":"2019","journal-title":"Mol. Ther."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.omtm.2021.12.003","article-title":"Safe and Efficient in Vivo Hematopoietic Stem Cell Transduction in Nonhuman Primates Using HDAd5\/35++ Vectors","volume":"24","author":"Li","year":"2022","journal-title":"Mol. Ther.-Methods Clin. Dev."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1038\/nmeth.3993","article-title":"A Multi-Functional AAV-CRISPR-Cas9 and Its Host Response","volume":"13","author":"Chew","year":"2016","journal-title":"Nat. Methods"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"3110","DOI":"10.3389\/fimmu.2019.03110","article-title":"Tetramer-Based Enrichment of Preexisting Anti-AAV8 CD8+ T Cells in Human Donors Allows the Detection of a TEMRA Subpopulation","volume":"10","author":"Vandamme","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.omtm.2020.11.015","article-title":"Low Incidence of Hepatocellular Carcinoma in Mice and Cats Treated with Systemic Adeno-Associated Viral Vectors","volume":"20","author":"Ferla","year":"2021","journal-title":"Mol. Ther.-Methods Clin. Dev."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.omtm.2017.11.007","article-title":"Emerging Issues in AAV-Mediated In Vivo Gene Therapy","volume":"8","author":"Colella","year":"2018","journal-title":"Mol. Ther.-Methods Clin. Dev."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s12967-018-1402-1","article-title":"Non-Viral Gene Delivery Systems for Tissue Repair and Regeneration","volume":"16","author":"Wu","year":"2018","journal-title":"J. Transl. Med."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.actbio.2016.10.015","article-title":"High Transfection Efficiency Promoted by Tailor-Made Cationic Tri-Block Copolymer-Based Nanoparticles","volume":"47","author":"Cordeiro","year":"2017","journal-title":"Acta Biomater."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.jconrel.2011.03.002","article-title":"Controlled Release of Cell-Permeable Gene Complex from Poly(L-Lactide) Scaffold for Enhanced Stem Cell Tissue Engineering","volume":"152","author":"Jung","year":"2011","journal-title":"J. Control. Release"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.jconrel.2014.05.055","article-title":"Major Degradable Polycations as Carriers for DNA and SiRNA","volume":"193","author":"Islam","year":"2014","journal-title":"J. Control. Release"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.ejpb.2016.06.017","article-title":"Development of Novel Recombinant Biomimetic Chimeric MPG-Based Peptide as Nanocarriers for Gene Delivery: Imitation of a Real Cargo","volume":"107","author":"Majidi","year":"2016","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_211","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez, E.F., Santos-Carballal, B., de Santi, C., Ramsey, J.M., MacLoughlin, R., Cryan, S.A., and Greene, C.M. (2018). Biopolymer-Based Nanoparticles for Cystic Fibrosis Lung Gene Therapy Studies. Materials, 11.","DOI":"10.3390\/ma11010122"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1038\/sj.gt.3301212","article-title":"Repeat Administration of DNA\/Liposomes to the Nasal Epithelium of Patients with Cystic Fibrosis","volume":"7","author":"Hyde","year":"2000","journal-title":"Gene Ther."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/S2213-2600(15)00245-3","article-title":"Repeated Nebulisation of Non-Viral CFTR Gene Therapy in Patients with Cystic Fibrosis: A Randomised, Double-Blind, Placebo-Controlled, Phase 2b Trial","volume":"3","author":"Alton","year":"2015","journal-title":"Lancet Respir. Med."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.jconrel.2017.09.044","article-title":"Highly Specific Delivery of SiRNA to Hepatocytes Circumvents Endothelial Cell-Mediated Lipid Nanoparticle-Associated Toxicity Leading to the Safe and Efficacious Decrease in the Hepatitis B Virus","volume":"266","author":"Sato","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_215","first-page":"79","article-title":"Lipid-Based Nanoparticle Technologies for Liver Targeting","volume":"154\u2013155","author":"Pauli","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1056\/NEJMoa2107454","article-title":"CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis","volume":"385","author":"Gillmore","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1038\/gt.2012.82","article-title":"Systemic Delivery of Triplex-Forming PNA and Donor DNA by Nanoparticles Mediates Site-Specific Genome Editing of Human Hematopoietic Cells in Vivo","volume":"20","author":"McNeer","year":"2013","journal-title":"Gene Ther."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"13304","DOI":"10.1038\/ncomms13304","article-title":"In Vivo Correction of Anaemia in \u03b2-Thalassemic Mice by \u03933PNA-Mediated Gene Editing with Nanoparticle Delivery","volume":"7","author":"Bahal","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"120580","DOI":"10.1016\/j.biomaterials.2020.120580","article-title":"PLGA-Nanoparticles for Intracellular Delivery of the CRISPR-Complex to Elevate Fetal Globin Expression in Erythroid Cells","volume":"268","author":"Cruz","year":"2021","journal-title":"Biomaterials"},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1089\/hum.2020.263","article-title":"Safe and Effective in Vivo Targeting and Gene Editing in Hematopoietic Stem Cells: Strategies for Accelerating Development","volume":"32","author":"Cannon","year":"2021","journal-title":"Hum. Gene Ther."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/s41591-018-0326-x","article-title":"Identification of Preexisting Adaptive Immunity to Cas9 Proteins in Humans","volume":"25","author":"Charlesworth","year":"2019","journal-title":"Nat. Med."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.omtm.2018.06.006","article-title":"Prevalence of Pre-Existing Antibodies to CRISPR-Associated Nuclease Cas9 in the USA Population","volume":"10","author":"Simhadri","year":"2018","journal-title":"Mol. Ther.-Methods Clin. Dev."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1038\/s41591-018-0204-6","article-title":"High Prevalence of Streptococcus Pyogenes Cas9-Reactive T Cells within the Adult Human Population","volume":"25","author":"Wagner","year":"2019","journal-title":"Nat. Med."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1038\/s41467-019-09693-x","article-title":"Multifunctional CRISPR-Cas9 with Engineered Immunosilenced Human T Cell Epitopes","volume":"10","author":"Ferdosi","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1016\/j.ymthe.2020.04.017","article-title":"AAV-CRISPR Gene Editing Is Negated by Pre-Existing Immunity to Cas9","volume":"28","author":"Li","year":"2020","journal-title":"Mol. Ther."},{"key":"ref_226","first-page":"704","article-title":"Prevalence of Serum IgG and Neutralizing Factors Against Adeno-Associated Virus (AAV) Types 1, 2, 5, 6, 8, and 9 in the Healthy Population: Implications for Gene Therapy Using AAV Vectors","volume":"712","author":"Monteilhet","year":"2010","journal-title":"Hum. Gene Ther."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/S0042-6822(03)00161-2","article-title":"Development of Adenovirus Serotype 35 as a Gene Transfer Vector","volume":"311","author":"Reddy","year":"2003","journal-title":"Virology"},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1056\/NEJMoa1407309","article-title":"Long-Term Safety and Efficacy of Factor IX Gene Therapy in Hemophilia B","volume":"371","author":"Nathwani","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1056\/NEJMoa2119913","article-title":"Phase 1-2 Trial of AAVS3 Gene Therapy in Patients with Hemophilia B","volume":"387","author":"Chowdary","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"475","DOI":"10.14348\/molcells.2015.0103","article-title":"Measuring and Reducing Off-Target Activities of Programmable Nucleases Including CRISPR-Cas9","volume":"38","author":"Koo","year":"2015","journal-title":"Mol. Cells"},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1038\/nrg.2016.28","article-title":"Defining and Improving the Genome-Wide Specificities of CRISPR-Cas9 Nucleases","volume":"17","author":"Shengdar","year":"2016","journal-title":"Nat. Rev. Genet."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1038\/s41586-018-0500-9","article-title":"In Vivo CRISPR Editing with No Detectable Genome-Wide Offtarget Mutations","volume":"561","author":"Akcakaya","year":"2018","journal-title":"Nature"},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"673022","DOI":"10.3389\/fgeed.2021.673022","article-title":"Off-Target Analysis in Gene Editing and Applications for Clinical Translation of CRISPR\/Cas9 in HIV-1 Therapy","volume":"3","author":"Atkins","year":"2021","journal-title":"Front. Genome Ed."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1038\/nbt.4192","article-title":"Repair of Double-Strand Breaks Induced by CRISPR\u2013Cas9 Leads to Large Deletions and Complex Rearrangements","volume":"36","author":"Kosicki","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"ref_235","doi-asserted-by":"crossref","unstructured":"Nahmad, A.D., Reuveni, E., Goldschmidt, E., Tenne, T., Liberman, M., Horovitz-Fried, M., Khosravi, R., Kobo, H., Reinstein, E., and Madi, A. (2022). Frequent Aneuploidy in Primary Human T Cells after CRISPR-Cas9 Cleavage. Nat. Biotechnol.","DOI":"10.1101\/2021.08.20.457092"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/12\/2222\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:27:41Z","timestamp":1760146061000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/12\/2222"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,27]]},"references-count":235,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["genes13122222"],"URL":"https:\/\/doi.org\/10.3390\/genes13122222","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,27]]}}}