{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T02:46:13Z","timestamp":1791081973867,"version":"4.1.0"},"reference-count":217,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"LEK-AM Pharmaceutical Company Ltd.","award":["2024\/ABM\/05\/KPO\/KPOD.07.07-IW.07-0242\/24-00"],"award-info":[{"award-number":["2024\/ABM\/05\/KPO\/KPOD.07.07-IW.07-0242\/24-00"]}]},{"DOI":"10.13039\/501100005888","name":"Medical University of Lodz","doi-asserted-by":"crossref","award":["503\/0-154-01\/503-01-001"],"award-info":[{"award-number":["503\/0-154-01\/503-01-001"]}],"id":[{"id":"10.13039\/501100005888","id-type":"DOI","asserted-by":"crossref"}]},{"award":["503\/0-154-01\/503-01-001"],"award-info":[{"award-number":["503\/0-154-01\/503-01-001"]}],"id":[{"id":"https:\/\/ror.org\/02t4ekc95","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>CRISPR\u2013Cas9 has progressed from an experimental tool to a therapeutic modality, marked by the first regulatory approvals of an ex vivo-edited autologous CD34+ hematopoietic stem cell product that induces fetal hemoglobin (CASGEVY\/exa-cel). In this narrative review, we synthesize modality-specific molecular diagnostic strategies used across early CRISPR clinical translation. In parallel, early clinical experience has begun to demonstrate the feasibility of in vivo editing, including subretinal delivery for CEP290-associated inherited retinal degeneration (EDIT-101 programme) and hepatocyte-targeted lipid nanoparticles (LNPs) for liver-derived targets such as transthyretin and plasma prekallikrein (KLKB1). As translation expands across hematologic, metabolic, ocular and oncology indications, development is increasingly constrained by the predictability and safety of editing outcomes, delivery-determined biodistribution and exposure time, and immune recognition of bacterial Cas9 orthologs and delivery components. We summarize diagnostic readouts for confirming patient genotype, quantifying on-target editing and expression changes, assessing off-target and structural outcomes using orthogonal assays, and monitoring clonal dynamics and immune responses during long-term follow-up. We also discuss how these readouts interface with CMC controls and regulatory expectations for advanced therapy medicinal products (ATMPs), highlighting the need for fit-for-purpose, standardized testing frameworks in early trials.<\/jats:p>","DOI":"10.3390\/cells15070644","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T15:14:43Z","timestamp":1775142883000},"page":"644","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["CRISPR\u2013Cas9 Therapeutics in Early Clinical Development: Delivery and Molecular Diagnostics"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0973-6052","authenticated-orcid":false,"given":"Adrianna","family":"Rutkowska","sequence":"first","affiliation":[{"name":"Department of Molecular Biology, Chair of Medical Biology, Medical University of Lodz, Zeligowskiego 7\/9 St., 90-752 Lodz, Poland"},{"name":"Department of Research and Development, LEK-AM Pharmaceutical Company Ltd., Inwestycyjna 7 St., 95-050 Konstantynow Lodzki, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1397-7166","authenticated-orcid":false,"given":"Tadeusz","family":"Str\u00f3zik","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Chair of Medical Biology, Medical University of Lodz, Zeligowskiego 7\/9 St., 90-752 Lodz, Poland"},{"name":"Department of Research and Development, LEK-AM Pharmaceutical Company Ltd., Inwestycyjna 7 St., 95-050 Konstantynow Lodzki, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4508-9534","authenticated-orcid":false,"given":"Tomasz","family":"Wasiak","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Chair of Medical Biology, Medical University of Lodz, Zeligowskiego 7\/9 St., 90-752 Lodz, Poland"},{"name":"Department of Research and Development, LEK-AM Pharmaceutical Company Ltd., Inwestycyjna 7 St., 95-050 Konstantynow Lodzki, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damian","family":"Ciunowicz","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Chair of Medical Biology, Medical University of Lodz, Zeligowskiego 7\/9 St., 90-752 Lodz, Poland"},{"name":"Department of Research and Development, LEK-AM Pharmaceutical Company Ltd., Inwestycyjna 7 St., 95-050 Konstantynow Lodzki, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Kapelan","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Chair of Medical Biology, Medical University of Lodz, Zeligowskiego 7\/9 St., 90-752 Lodz, Poland"},{"name":"Student Scientific Circle at the Department of Molecular Biology, Chair of Medical Biology, Medical University of Lodz, Zeligowskiego 7\/9 St., 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Szczepaniak","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Chair of Medical Biology, Medical University of Lodz, Zeligowskiego 7\/9 St., 90-752 Lodz, Poland"},{"name":"Student Scientific Circle at the Department of Molecular Biology, Chair of Medical Biology, Medical University of Lodz, Zeligowskiego 7\/9 St., 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliusz","family":"Sosnowski","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Chair of Medical Biology, Medical University of Lodz, Zeligowskiego 7\/9 St., 90-752 Lodz, Poland"},{"name":"Student Scientific Circle at the Department of Molecular Biology, Chair of Medical Biology, Medical University of Lodz, Zeligowskiego 7\/9 St., 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weronika","family":"Go\u015bli\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Chair of Medical Biology, Medical University of Lodz, Zeligowskiego 7\/9 St., 90-752 Lodz, Poland"},{"name":"Student Scientific Circle at the Department of Molecular Biology, Chair of Medical Biology, Medical University of Lodz, Zeligowskiego 7\/9 St., 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakub","family":"Bartkowiak","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Chair of Medical Biology, Medical University of Lodz, Zeligowskiego 7\/9 St., 90-752 Lodz, Poland"},{"name":"Student Scientific Circle at the Department of Molecular Biology, Chair of Medical Biology, Medical University of Lodz, Zeligowskiego 7\/9 St., 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata","family":"Budny-Lewandowska","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Chair of Medical Biology, Medical University of Lodz, Zeligowskiego 7\/9 St., 90-752 Lodz, Poland"},{"name":"Student Scientific Circle at the Department of Molecular Biology, Chair of Medical Biology, Medical University of Lodz, Zeligowskiego 7\/9 St., 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrycja","family":"Anto\u0144czyk","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Chair of Medical Biology, Medical University of Lodz, Zeligowskiego 7\/9 St., 90-752 Lodz, Poland"},{"name":"Student Scientific Circle at the Department of Molecular Biology, Chair of Medical Biology, Medical University of Lodz, Zeligowskiego 7\/9 St., 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Markiewicz","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Chair of Medical Biology, Medical University of Lodz, Zeligowskiego 7\/9 St., 90-752 Lodz, Poland"},{"name":"Student Scientific Circle at the Department of Molecular Biology, Chair of Medical Biology, Medical University of Lodz, Zeligowskiego 7\/9 St., 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Gustaw","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Chair of Medical Biology, Medical University of Lodz, Zeligowskiego 7\/9 St., 90-752 Lodz, Poland"},{"name":"Student Scientific Circle at the Department of Molecular Biology, Chair of Medical Biology, Medical University of Lodz, Zeligowskiego 7\/9 St., 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4193-8997","authenticated-orcid":false,"given":"Kamil","family":"Filiks","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Chair of Medical Biology, Medical University of Lodz, Zeligowskiego 7\/9 St., 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2607-1892","authenticated-orcid":false,"given":"Maria","family":"Jask\u00f3lska","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Chair of Medical Biology, Medical University of Lodz, Zeligowskiego 7\/9 St., 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewelina","family":"Stoczy\u0144ska-Fidelus","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Chair of Medical Biology, Medical University of Lodz, Zeligowskiego 7\/9 St., 90-752 Lodz, 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Nobel Prize in Chemistry 2020: Genetic Scissors: A Tool for Rewriting the Code of Life, The Royal Swedish Academy of Sciences. Available online: https:\/\/www.nobelprize.org\/prizes\/chemistry\/2020\/press-release\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.1099\/mic.0.28048-0","article-title":"Clustered regularly interspaced short palindrome repeats (CRISPRs) have spacers of extrachromosomal origin","volume":"151","author":"Bolotin","year":"2005","journal-title":"Microbiology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1099\/mic.0.27437-0","article-title":"CRISPR elements in Yersinia pestis acquire new repeats by preferential uptake of bacteriophage DNA, and provide additional tools for evolutionary studies","volume":"151","author":"Pourcel","year":"2005","journal-title":"Microbiology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1007\/s00239-004-0046-3","article-title":"Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements","volume":"60","author":"Mojica","year":"2005","journal-title":"J. Mol. Evol."},{"key":"ref_5","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_6","doi-asserted-by":"crossref","unstructured":"Ates, I., Rathbone, T., Stuart, C., Bridges, P.H., and Cottle, R.N. (2020). Delivery Approaches for Therapeutic Genome Editing and Challenges. Genes, 11.","DOI":"10.3390\/genes11101113"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.omtn.2019.02.027","article-title":"Genome-Editing Technologies: Concept, Pros, and Cons of Various Genome-Editing Techniques and Bioethical Concerns for Clinical Application","volume":"16","author":"Khan","year":"2019","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_8","unstructured":"European Medicines Agency (2026, March 08). Guideline on Quality, Non-Clinical and Clinical Requirements for Investigational Advanced Therapy Medicinal Products in Clinical Trials, Available online: https:\/\/www.ema.europa.eu\/en\/guideline-quality-non-clinical-clinical-requirements-investigational-advanced-therapy-medicinal-products-clinical-trials-scientific-guideline."},{"key":"ref_9","unstructured":"European Medicines Agency (2026, March 08). Advanced Therapy Medicinal Products: Overview, Available online: https:\/\/www.ema.europa.eu\/en\/human-regulatory-overview\/advanced-therapy-medicinal-products-overview."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1056\/NEJMoa2031054","article-title":"CRISPR-Cas9 Gene Editing for Sickle Cell Disease and beta-Thalassemia","volume":"384","author":"Frangoul","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_11","unstructured":"Vertex Pharmaceuticals Incorporated (2026). Highlights of Prescribing Information. Casgevy (Exagamglogene Autotemcel), Suspension for Intravenous Infusion. Initial U.S. Approval: 2023, Vertex Pharmaceuticals Incorporated. Available online: https:\/\/pi.vrtx.com\/files\/uspi_exagamglogene_autotemcel.pdf."},{"key":"ref_12","unstructured":"European Medicines Agency (2026, March 08). Casgevy, Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/casgevy."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1056\/NEJMoa2309915","article-title":"Gene Editing for CEP290-Associated Retinal Degeneration","volume":"390","author":"Pierce","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_14","first-page":"1","article-title":"Marketing Regulatory Oversight of Advanced Therapy Medicinal Products in Europe","volume":"1430","author":"Herberts","year":"2023","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_15","first-page":"367","article-title":"Regulatory Aspects for Approval of Advanced Therapy Medicinal Products in the EU","volume":"284","author":"Buhrer","year":"2024","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Alaburde, S., Ivaska, J., Kaspute, G., and Ivaskiene, T. (2025). Impact of regulatory measures on the approval timelines of advanced therapy medicinal products by the European Medicines Agency. Front. Med., 12.","DOI":"10.3389\/fmed.2025.1623689"},{"key":"ref_17","unstructured":"EUR-Lex (2023). Proposal for a Directive of the European Parliament and of the Council on the Union Code Relating to Medicinal Products for Human Use, and Repealing Directive 2001\/83\/EC and Directive 2009\/35\/EC, EUR-Lex. Available online: https:\/\/eur-lex.europa.eu\/legal-content\/EN\/TXT\/?uri=CELEX:52023PC0192."},{"key":"ref_18","unstructured":"European Commission (2026, March 08). Reform of the EU Pharmaceutical Legislation, Available online: https:\/\/health.ec.europa.eu\/medicinal-products\/legal-framework-governing-medicinal-products-human-use-eu\/reform-eu-pharmaceutical-legislation_en."},{"key":"ref_19","unstructured":"(2026, March 08). Clinicaltrials.Gov, Available online: https:\/\/clinicaltrials.gov\/."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1038\/d41586-024-04105-7","article-title":"Human embryo editing against disease is unsafe and unproven-despite rosy predictions","volume":"637","author":"Carmi","year":"2025","journal-title":"Nature"},{"key":"ref_21","first-page":"17378","article-title":"Chinese scientists genetically modify human embryos","volume":"22","author":"Cyranoski","year":"2015","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1038\/519410a","article-title":"Don\u2019t edit the human germ line","volume":"519","author":"Lanphier","year":"2015","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s13238-015-0153-5","article-title":"CRISPR\/Cas9-mediated gene editing in human tripronuclear zygotes","volume":"6","author":"Liang","year":"2015","journal-title":"Protein Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1016\/j.stemcr.2021.05.012","article-title":"ISSCR Guidelines for Stem Cell Research and Clinical Translation: The 2021 update","volume":"16","author":"Anthony","year":"2021","journal-title":"Stem Cell Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5429","DOI":"10.1128\/jb.169.12.5429-5433.1987","article-title":"Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product","volume":"169","author":"Ishino","year":"1987","journal-title":"J. Bacteriol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1111\/j.1365-2958.1993.tb00976.x","article-title":"Nature of DNA polymorphism in the direct repeat cluster of Mycobacterium tuberculosis; application for strain differentiation by a novel typing method","volume":"10","author":"Groenen","year":"1993","journal-title":"Mol. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1046\/j.1365-2958.2000.01838.x","article-title":"Biological significance of a family of regularly spaced repeats in the genomes of Archaea, Bacteria and mitochondria","volume":"36","author":"Mojica","year":"2000","journal-title":"Mol. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1046\/j.1365-2958.2002.02839.x","article-title":"Identification of genes that are associated with DNA repeats in prokaryotes","volume":"43","author":"Jansen","year":"2002","journal-title":"Mol. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1126\/science.1179555","article-title":"CRISPR\/Cas, the immune system of bacteria and archaea","volume":"327","author":"Horvath","year":"2010","journal-title":"Science"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1016\/j.cell.2014.05.010","article-title":"Development and applications of CRISPR-Cas9 for genome engineering","volume":"157","author":"Hsu","year":"2014","journal-title":"Cell"},{"key":"ref_31","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_32","doi-asserted-by":"crossref","first-page":"eaba7365","DOI":"10.1126\/science.aba7365","article-title":"CRISPR-engineered T cells in patients with refractory cancer","volume":"367","author":"Stadtmauer","year":"2020","journal-title":"Science"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s40291-024-00696-z","article-title":"Exagamglogene Autotemcel: First Approval","volume":"28","author":"Hoy","year":"2024","journal-title":"Mol. Diagn. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1038\/s41587-024-02472-0","article-title":"CRISPR Nobelists surrender their own European patents","volume":"42","author":"Harrison","year":"2024","journal-title":"Nat. Biotechnol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1038\/s12276-025-01514-0","article-title":"CRISPR-based functional genomics tools in vertebrate models","volume":"57","author":"Varshney","year":"2025","journal-title":"Exp. Mol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Grissa, I., Vergnaud, G., and Pourcel, C. (2007). The CRISPRdb database and tools to display CRISPRs and to generate dictionaries of spacers and repeats. BMC Bioinform., 8.","DOI":"10.1186\/1471-2105-8-172"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1093\/nar\/30.2.482","article-title":"A DNA repair system specific for thermophilic Archaea and bacteria predicted by genomic context analysis","volume":"30","author":"Makarova","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Haft, D.H., Selengut, J., Mongodin, E.F., and Nelson, K.E. (2005). A guild of 45 CRISPR-associated (Cas) protein families and multiple CRISPR\/Cas subtypes exist in prokaryotic genomes. PLoS Comput. Biol., 1.","DOI":"10.1371\/journal.pcbi.0010060"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1745-6150-1-7","article-title":"A putative RNA-interference-based immune system in prokaryotes: Computational analysis of the predicted enzymatic machinery, functional analogies with eukaryotic RNAi, and hypothetical mechanisms of action","volume":"1","author":"Makarova","year":"2006","journal-title":"Biol. Direct"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1126\/science.1138140","article-title":"CRISPR provides acquired resistance against viruses in prokaryotes","volume":"315","author":"Barrangou","year":"2007","journal-title":"Science"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/s41579-019-0299-x","article-title":"Evolutionary classification of CRISPR-Cas systems: A burst of class 2 and derived variants","volume":"18","author":"Makarova","year":"2020","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1038\/ncomms1937","article-title":"Molecular memory of prior infections activates the CRISPR\/Cas adaptive bacterial immunity system","volume":"3","author":"Datsenko","year":"2012","journal-title":"Nat. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"E2579","DOI":"10.1073\/pnas.1208507109","article-title":"Cas9-crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria","volume":"109","author":"Gasiunas","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1038\/nsmb.2820","article-title":"Cas1-Cas2 complex formation mediates spacer acquisition during CRISPR-Cas adaptive immunity","volume":"21","author":"Nunez","year":"2014","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"841","DOI":"10.4161\/rna.24203","article-title":"crRNA and tracrRNA guide Cas9-mediated DNA interference in Streptococcus thermophilus","volume":"10","author":"Karvelis","year":"2013","journal-title":"RNA Biol."},{"key":"ref_46","first-page":"259","article-title":"In Vitro Pre-validation of Gene Editing by CRISPR\/Cas9 Ribonucleoprotein","volume":"11","author":"Mehravar","year":"2019","journal-title":"Avicenna J. Med. Biotechnol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1177\/2472630320922813","article-title":"Core Hairpin Structure of SpCas9 sgRNA Functions in a Sequence- and Spatial Conformation-Dependent Manner","volume":"26","author":"Jiang","year":"2021","journal-title":"SLAS Technol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Rawashdeh, O., Rawashdeh, R.Y., Kebede, T., Kapp, D., and Ralescu, A. (2022). Bio-informatic analysis of CRISPR protospacer adjacent motifs (PAMs) in T4 genome. BMC Genom. Data, 23.","DOI":"10.1186\/s12863-022-01056-8"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"23549","DOI":"10.1038\/srep23549","article-title":"Systematic quantification of HDR and NHEJ reveals effects of locus, nuclease, and cell type on genome-editing","volume":"6","author":"Miyaoka","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"371","DOI":"10.34172\/bi.2022.23871","article-title":"Advance trends in targeting homology-directed repair for accurate gene editing: An inclusive review of small molecules and modified CRISPR-Cas9 systems","volume":"12","author":"Shams","year":"2022","journal-title":"BioImpacts BI"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1038\/s41467-019-09005-3","article-title":"A gRNA-tRNA array for CRISPR-Cas9 based rapid multiplexed genome editing in Saccharomyces cerevisiae","volume":"10","author":"Zhang","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"124455","DOI":"10.1016\/j.talanta.2023.124455","article-title":"CRISPR\/deadCas9-based high-throughput gene doping analysis (HiGDA): A proof of concept for exogenous human erythropoietin gene doping detection","volume":"258","author":"Yi","year":"2023","journal-title":"Talanta"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1056\/NEJMoa2309673","article-title":"Exagamglogene Autotemcel for Transfusion-Dependent beta-Thalassemia","volume":"390","author":"Locatelli","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_54","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_55","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1056\/NEJMoa2510209","article-title":"Nexiguran Ziclumeran Gene Editing in Hereditary ATTR with Polyneuropathy","volume":"393","author":"Gillmore","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1056\/NEJMoa2412309","article-title":"CRISPR-Cas9 Gene Editing with Nexiguran Ziclumeran for ATTR Cardiomyopathy","volume":"391","author":"Fontana","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_57","unstructured":"ClinicalTrials (2023). A Single-Arm, Open-Label Exploratory Clinical Study to Assess the Preliminary Safety of the Gene Editing Drug ZVS203e for the Management of Retinitis Pigmentosa Caused by Mutations in the RHO Gene."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"6267","DOI":"10.1038\/s41467-021-26518-y","article-title":"Self-inactivating, all-in-one AAV vectors for precision Cas9 genome editing via homology-directed repair in vivo","volume":"12","author":"Ibraheim","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4439","DOI":"10.1038\/s41467-019-12449-2","article-title":"High levels of AAV vector integration into CRISPR-induced DNA breaks","volume":"10","author":"Hanlon","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4122","DOI":"10.1016\/j.ymthe.2024.09.032","article-title":"AAV vector-derived elements integrate into Cas9-generated double-strand breaks and disrupt gene transcription","volume":"32","author":"Bazick","year":"2024","journal-title":"Mol. Ther."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"gkae1213","DOI":"10.1093\/nar\/gkae1213","article-title":"Precision genome editing using combinatorial viral vector delivery of CRISPR-Cas9 nucleases and donor DNA constructs","volume":"53","author":"Li","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1038\/s41587-024-02437-3","article-title":"Lung and liver editing by lipid nanoparticle delivery of a stable CRISPR-Cas9 ribonucleoprotein","volume":"43","author":"Chen","year":"2025","journal-title":"Nat. Biotechnol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Han, X., Xu, Y., Ricciardi, A., Xu, J., Palanki, R., Chowdhary, V., Xue, L., Gong, N., Alameh, M.G., and Peranteau, W.H. (2025). Plug-and-play assembly of biodegradable ionizable lipids for potent mRNA delivery and gene editing in vivo. bioRxiv.","DOI":"10.1101\/2025.02.25.640222"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"9880","DOI":"10.1093\/nar\/gkad702","article-title":"Guide-specific loss of efficiency and off-target reduction with Cas9 variants","volume":"51","author":"Zhang","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e2307796121","DOI":"10.1073\/pnas.2307796121","article-title":"Targeted nonviral delivery of genome editors in vivo","volume":"121","author":"Tsuchida","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"7208","DOI":"10.1038\/s41467-025-62606-z","article-title":"The hidden risks of CRISPR\/Cas: Structural variations and genome integrity","volume":"16","author":"Aussel","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1038\/s41587-024-02488-6","article-title":"Genome editing with the HDR-enhancing DNA-PKcs inhibitor AZD7648 causes large-scale genomic alterations","volume":"43","author":"Cullot","year":"2025","journal-title":"Nat. Biotechnol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1038\/s41592-023-01840-z","article-title":"Improving the sensitivity of in vivo CRISPR off-target detection with DISCOVER-Seq","volume":"20","author":"Zou","year":"2023","journal-title":"Nat. Methods"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e87","DOI":"10.1093\/nar\/gkae759","article-title":"Learning to quantify uncertainty in off-target activity for CRISPR guide RNAs","volume":"52","author":"Minary","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1056\/NEJMoa2309676","article-title":"Exagamglogene Autotemcel for Severe Sickle Cell Disease","volume":"390","author":"Frangoul","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1056\/NEJMoa2309149","article-title":"CRISPR-Cas9 In Vivo Gene Editing of KLKB1 for Hereditary Angioedema","volume":"390","author":"Longhurst","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1126\/science.1088547","article-title":"LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1","volume":"302","author":"Schmidt","year":"2003","journal-title":"Science"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1056\/NEJMoa2405734","article-title":"CRISPR-Based Therapy for Hereditary Angioedema","volume":"392","author":"Cohn","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1038\/s41587-021-00933-4","article-title":"In vivo adenine base editing of PCSK9 in macaques reduces LDL cholesterol levels","volume":"39","author":"Rothgangl","year":"2021","journal-title":"Nat. Biotechnol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1161\/CIRCULATIONAHA.122.062132","article-title":"Efficacy and Safety of an Investigational Single-Course CRISPR Base-Editing Therapy Targeting PCSK9 in Nonhuman Primate and Mouse Models","volume":"147","author":"Lee","year":"2023","journal-title":"Circulation"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/s41586-021-03534-y","article-title":"In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates","volume":"593","author":"Musunuru","year":"2021","journal-title":"Nature"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"5060","DOI":"10.1038\/s41467-020-18875-x","article-title":"In vivo CRISPR\/Cas9 targeting of fusion oncogenes for selective elimination of cancer cells","volume":"11","author":"Martin","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Dudka, W., Hoser, G., Mondal, S.S., Turos-Korgul, L., Swatler, J., Kusio-Kobialka, M., Wolczyk, M., Klejman, A., Brewinska-Olchowik, M., and Kominek, A. (2022). Targeting integrated stress response with ISRIB combined with imatinib treatment attenuates RAS\/RAF\/MAPK and STAT5 signaling and eradicates chronic myeloid leukemia cells. BMC Cancer, 22.","DOI":"10.1186\/s12885-022-10289-w"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3642","DOI":"10.1128\/MCB.00814-14","article-title":"Plk1 phosphorylation of PTEN causes a tumor-promoting metabolic state","volume":"34","author":"Li","year":"2014","journal-title":"Mol. Cell. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1038\/s41467-017-01647-5","article-title":"Polo-like kinase 1 coordinates biosynthesis during cell cycle progression by directly activating pentose phosphate pathway","volume":"8","author":"Ma","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"eabc9450","DOI":"10.1126\/sciadv.abc9450","article-title":"CRISPR-Cas9 genome editing using targeted lipid nanoparticles for cancer therapy","volume":"6","author":"Rosenblum","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"eabm8011","DOI":"10.1126\/sciadv.abm8011","article-title":"Blood-brain barrier-penetrating single CRISPR-Cas9 nanocapsules for effective and safe glioblastoma gene therapy","volume":"8","author":"Zou","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"eaav7199","DOI":"10.1126\/sciadv.aav7199","article-title":"Near-infrared upconversion-activated CRISPR-Cas9 system: A remote-controlled gene editing platform","volume":"5","author":"Pan","year":"2019","journal-title":"Sci. Adv."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1038\/s41374-018-0056-1","article-title":"Specific targeting of point mutations in EGFR L858R-positive lung cancer by CRISPR\/Cas9","volume":"98","author":"Cheung","year":"2018","journal-title":"Lab Investig."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.ccr.2010.05.025","article-title":"A synthetic lethal interaction between K-Ras oncogenes and Cdk4 unveils a therapeutic strategy for non-small cell lung carcinoma","volume":"18","author":"Puyol","year":"2010","journal-title":"Cancer Cell"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"eadk8264","DOI":"10.1126\/sciadv.adk8264","article-title":"Cryo-shocked tumor cells deliver CRISPR-Cas9 for lung cancer regression by synthetic lethality","volume":"10","author":"Liu","year":"2024","journal-title":"Sci. Adv."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1186\/s12935-024-03467-2","article-title":"Comprehensive analysis, diagnosis, prognosis, and cordycepin (CD) regulations for GSDME expressions in pan-cancers","volume":"24","author":"Fu","year":"2024","journal-title":"Cancer Cell Int."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1038\/s41467-023-36550-9","article-title":"A cooperative nano-CRISPR scaffold potentiates immunotherapy via activation of tumour-intrinsic pyroptosis","volume":"14","author":"Wang","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/s41417-019-0131-9","article-title":"Synergistic antitumor effect on cervical cancer by rational combination of PD1 blockade and CRISPR-Cas9-mediated HPV knockout","volume":"27","author":"Zhen","year":"2020","journal-title":"Cancer Gene Ther."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"11240","DOI":"10.1080\/21655979.2022.2064205","article-title":"Everolimus (RAD001) combined with programmed death-1 (PD-1) blockade enhances radiosensitivity of cervical cancer and programmed death-ligand 1 (PD-L1) expression by blocking the phosphoinositide 3-kinase (PI3K)\/protein kinase B (AKT)\/mammalian target of rapamycin (mTOR)\/S6 kinase 1 (S6K1) pathway","volume":"13","author":"Song","year":"2022","journal-title":"Bioengineered"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.tranon.2016.10.002","article-title":"In Vitro and In Vivo Synergistic Therapeutic Effect of Cisplatin with Human Papillomavirus16 E6\/E7 CRISPR\/Cas9 on Cervical Cancer Cell Line","volume":"9","author":"Zhen","year":"2016","journal-title":"Transl. Oncol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.ebiom.2016.11.013","article-title":"IDO1 is an Integral Mediator of Inflammatory Neovascularization","volume":"14","author":"Mondal","year":"2016","journal-title":"eBioMedicine"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"7903","DOI":"10.1038\/s41467-022-35580-z","article-title":"Design of a self-driven probiotic-CRISPR\/Cas9 nanosystem for sono-immunometabolic cancer therapy","volume":"13","author":"Yu","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"4647","DOI":"10.1038\/s41467-023-40345-3","article-title":"A bimetallic nanoplatform for STING activation and CRISPR\/Cas mediated depletion of the methionine transporter in cancer cells restores anti-tumor immune responses","volume":"14","author":"Huang","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s13045-019-0760-3","article-title":"Tumor-associated macrophages in tumor metastasis: Biological roles and clinical therapeutic applications","volume":"12","author":"Lin","year":"2019","journal-title":"J. Hematol. Oncol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1038\/s41467-024-44941-9","article-title":"Bacterial protoplast-derived nanovesicles carrying CRISPR-Cas9 tools re-educate tumor-associated macrophages for enhanced cancer immunotherapy","volume":"15","author":"Zhao","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/s41434-020-0128-x","article-title":"Cancer gene therapy by NF-kappaB-activated cancer cell-specific expression of CRISPR\/Cas9 targeting telomeres","volume":"27","author":"Dai","year":"2020","journal-title":"Gene Ther."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"4110","DOI":"10.1038\/s41388-019-0707-8","article-title":"Cancer therapy with a CRISPR-assisted telomerase-activating gene expression system","volume":"38","author":"Dai","year":"2019","journal-title":"Oncogene"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"5266","DOI":"10.1038\/s41467-024-49450-3","article-title":"In vivo CRISPR screens reveal SCAF1 and USP15 as drivers of pancreatic cancer","volume":"15","author":"Martinez","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Oktriani, R., Pirona, A.C., Kalmar, L., Rahadian, A.S., Miao, B., Bauer, A.S., Hoheisel, J.D., Boettcher, M., and Du, H. (2024). Genome-Wide CRISPR Screen Identifies Genes Involved in Metastasis of Pancreatic Ductal Adenocarcinoma. Cancers, 16.","DOI":"10.3390\/cancers16213684"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"15912","DOI":"10.1038\/s41598-024-66244-1","article-title":"A whole-genome CRISPR screen identifies the spindle accessory checkpoint as a locus of nab-paclitaxel resistance in a pancreatic cancer cell line","volume":"14","author":"Mondal","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1158\/0008-5472.CAN-25-1835","article-title":"CRISPR-Cas9 Screening Identifies Resistance Mechanisms to KRAS Inhibition in Pancreatic Cancer","volume":"86","author":"Long","year":"2025","journal-title":"Cancer Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1007\/s00432-024-05837-9","article-title":"CRISPR\/Cas9-based genome-wide screening for metastasis ability identifies FCGR1A regulating the metastatic process of ovarian cancer by targeting LSP1","volume":"150","author":"Qi","year":"2024","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Perampalam, P., McDonald, J.I., and Dick, F.A. (2024). GO-CRISPR: A highly controlled workflow to discover gene essentiality in loss-of-function screens. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0315923"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1007\/s13258-024-01544-4","article-title":"Transcriptome analysis of the effect of HERV-K env gene knockout in ovarian cancer cell lines","volume":"46","author":"Ko","year":"2024","journal-title":"Genes Genom."},{"key":"ref_106","unstructured":"ClinicalTrials (2023). MAGNITUDE: A Phase 3, Multinational, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of NTLA-2001 in Participants with Transthyretin Amyloidosis with Cardiomyopathy (ATTR-CM)."},{"key":"ref_107","unstructured":"(2021). Phase 1\/2 Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NTLA-2002 in Adults with Hereditary Angioedema (HAE), ClinicalTrials."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1056\/NEJMoa2511778","article-title":"Phase 1 Trial of CRISPR-Cas9 Gene Editing Targeting ANGPTL3","volume":"393","author":"Laffin","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_109","unstructured":"(2026, March 08). Australian New Zealand Clinical Trials Registry. ACTRN12623001095651p. Available online: https:\/\/www.anzctr.org.au\/Trial\/Registration\/TrialReview.aspx?id=386521."},{"key":"ref_110","unstructured":"(2026, March 08). Beam Therapeutics Presents Additional Data for BEAM-302 in Alpha-1 Antitrypsin Deficiency (AATD) at 2025 Alpha-1 Foundation 7th Global Research Conference and 10th Patient Congress. Available online: https:\/\/www.globenewswire.com\/news-release\/2025\/04\/05\/3056264\/0\/en\/beam-therapeutics-presents-additional-data-for-beam-302-in-alpha-1-antitrypsin-deficiency-aatd-at-2025-alpha-1-foundation-7th-global-research-conference-and-10th-patient-congress.html."},{"key":"ref_111","unstructured":"ClinicalTrials (2024). A Phase 1\/2 Dose-Exploration and Dose-Expansion Study to Evaluate the Safety and Efficacy of BEAM-302 in Adult Patients With Alpha-1 Antitrypsin Deficiency (AATD)-Associated Lung Disease and\/or Liver Disease."},{"key":"ref_112","unstructured":"(2026, March 08). Verve Therapeutics Announces Positive Initial Data from the Heart-2 Phase 1b Clinical Trial of VERVE-102, an In Vivo Base Editing Medicine Targeting PCSK9. Available online: https:\/\/www.globenewswire.com\/news-release\/2025\/04\/14\/3060774\/0\/en\/Verve-Therapeutics-Announces-Positive-Initial-Data-from-the-Heart-2-Phase-1b-Clinical-Trial-of-VERVE-102-an-In-Vivo-Base-Editing-Medicine-Targeting-PCSK9.html."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1080\/13543784.2024.2369747","article-title":"VERVE-101, a CRISPR base-editing therapy designed to permanently inactivate hepatic PCSK9 and reduce LDL-cholesterol","volume":"33","author":"Hooper","year":"2024","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/s43856-025-00816-8","article-title":"Rescue of lysosomal acid lipase deficiency in mice by rAAV8 liver gene transfer","volume":"5","author":"Laurent","year":"2025","journal-title":"Commun. Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1038\/s41591-022-01906-z","article-title":"CRISPR-Cas9-mediated gene editing of the BCL11A enhancer for pediatric beta(0)\/beta(0) transfusion-dependent beta-thalassemia","volume":"28","author":"Fu","year":"2022","journal-title":"Nat. Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1056\/NEJMoa2215643","article-title":"CRISPR-Cas9 Editing of the HBG1 and HBG2 Promoters to Treat Sickle Cell Disease","volume":"389","author":"Sharma","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"eaay9392","DOI":"10.1126\/sciadv.aay9392","article-title":"Editing a gamma-globin repressor binding site restores fetal hemoglobin synthesis and corrects the sickle cell disease phenotype","volume":"6","author":"Weber","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"eabf2444","DOI":"10.1126\/scitranslmed.abf2444","article-title":"Development of beta-globin gene correction in human hematopoietic stem cells as a potential durable treatment for sickle cell disease","volume":"13","author":"Lattanzi","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"15551","DOI":"10.1038\/s41598-022-19934-7","article-title":"Genetic correction of haemoglobin E in an immortalised haemoglobin E\/beta-thalassaemia cell line using the CRISPR\/Cas9 system","volume":"12","author":"Trakarnsanga","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.stem.2019.11.002","article-title":"High-Efficiency, Selection-free Gene Repair in Airway Stem Cells from Cystic Fibrosis Patients Rescues CFTR Function in Differentiated Epithelia","volume":"26","author":"Vaidyanathan","year":"2020","journal-title":"Cell Stem Cell"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.ymthe.2021.03.023","article-title":"Targeted replacement of full-length CFTR in human airway stem cells by CRISPR-Cas9 for pan-mutation correction in the endogenous locus","volume":"30","author":"Vaidyanathan","year":"2022","journal-title":"Mol. Ther. J. Am. Soc. Gene Ther."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.omtn.2019.02.006","article-title":"Efficient Gene Editing at Major CFTR Mutation Loci","volume":"16","author":"Ruan","year":"2019","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1016\/j.ymthe.2023.03.004","article-title":"Functional restoration of a CFTR splicing mutation through RNA delivery of CRISPR adenine base editor","volume":"31","author":"Amistadi","year":"2023","journal-title":"Mol. Ther. J. Am. Soc. Gene Ther."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.stem.2015.07.001","article-title":"Functional Correction of Large Factor VIII Gene Chromosomal Inversions in Hemophilia A Patient-Derived iPSCs Using CRISPR-Cas9","volume":"17","author":"Park","year":"2015","journal-title":"Cell Stem Cell"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-019-0243-1","article-title":"Restoration of FVIII expression by targeted gene insertion in the FVIII locus in hemophilia A patient-derived iPSCs","volume":"51","author":"Sung","year":"2019","journal-title":"Exp. Mol. Med."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"829","DOI":"10.3324\/haematol.2019.224063","article-title":"CRISPR\/Cas9-mediated knockin of human factor IX into swine factor IX locus effectively alleviates bleeding in hemophilia B pigs","volume":"106","author":"Chen","year":"2021","journal-title":"Haematologica"},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Hu, Z., Wu, Y., Xiao, R., Zhao, J., Chen, Y., Wu, L., Zhou, M., and Liang, D. (2023). Correction of F8 intron 1 inversion in hemophilia A patient-specific iPSCs by CRISPR\/Cas9 mediated gene editing. Front. Genet., 14.","DOI":"10.3389\/fgene.2023.1115831"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"eabj6901","DOI":"10.1126\/sciadv.abj6901","article-title":"In vivo delivery of CRISPR-Cas9 using lipid nanoparticles enables antithrombin gene editing for sustainable hemophilia A and B therapy","volume":"8","author":"Han","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1089\/hum.2017.252","article-title":"Curative Ex Vivo Hepatocyte-Directed Gene Editing in a Mouse Model of Hereditary Tyrosinemia Type 1","volume":"29","author":"VanLith","year":"2018","journal-title":"Hum. Gene Ther."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1002\/hep4.1315","article-title":"Ex Vivo Hepatocyte Reprograming Promotes Homology-Directed DNA Repair to Correct Metabolic Disease in Mice After Transplantation","volume":"3","author":"VanLith","year":"2019","journal-title":"Hepatol. Commun."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"12642","DOI":"10.1038\/ncomms12642","article-title":"Reprogramming metabolic pathways in vivo with CRISPR\/Cas9 genome editing to treat hereditary tyrosinaemia","volume":"7","author":"Pankowicz","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1016\/j.ymthe.2020.11.023","article-title":"CRISPR\/Cas9-Mediated Gene Correction in Newborn Rabbits with Hereditary Tyrosinemia Type I","volume":"29","author":"Li","year":"2021","journal-title":"Mol. Ther. J. Am. Soc. Gene Ther."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/nbt.2884","article-title":"Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype","volume":"32","author":"Yin","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.omtm.2019.12.004","article-title":"AAV-Mediated CRISPR\/Cas9 Gene Editing in Murine Phenylketonuria","volume":"17","author":"Richards","year":"2020","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1016\/j.ajhg.2023.10.005","article-title":"Efficient in vivo prime editing corrects the most frequent phenylketonuria variant, associated with high unmet medical need","volume":"110","author":"Brooks","year":"2023","journal-title":"Am. J. Hum. Genet."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"35794","DOI":"10.1038\/srep35794","article-title":"CRISPR RNA-guided FokI nucleases repair a PAH variant in a phenylketonuria model","volume":"6","author":"Pan","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"3451","DOI":"10.1038\/s41467-023-39246-2","article-title":"Rapid and definitive treatment of phenylketonuria in variant-humanized mice with corrective editing","volume":"14","author":"Brooks","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1016\/j.ymthe.2020.12.027","article-title":"Correction of metabolic abnormalities in a mouse model of glycogen storage disease type Ia by CRISPR\/Cas9-based gene editing","volume":"29","author":"Arnaoutova","year":"2021","journal-title":"Mol. Ther. J. Am. Soc. Gene Ther."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"9729","DOI":"10.1038\/s41467-024-54108-1","article-title":"Base-editing corrects metabolic abnormalities in a humanized mouse model for glycogen storage disease type-Ia","volume":"15","author":"Arnaoutova","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1002\/jimd.12660","article-title":"CRISPR\/Cas9-based double-strand oligonucleotide insertion strategy corrects metabolic abnormalities in murine glycogen storage disease type-Ia","volume":"46","author":"Samanta","year":"2023","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"4045","DOI":"10.1038\/s41467-019-11962-8","article-title":"Human genome-edited hematopoietic stem cells phenotypically correct Mucopolysaccharidosis type I","volume":"10","author":"Scharenberg","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.ejpb.2017.10.017","article-title":"Gene editing of MPS I human fibroblasts by co-delivery of a CRISPR\/Cas9 plasmid and a donor oligonucleotide using nanoemulsions as nonviral carriers","volume":"122","author":"Schuh","year":"2018","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.gene.2018.08.004","article-title":"CRISPR-Cas9-mediated gene editing in human MPS I fibroblasts","volume":"678","author":"Schuh","year":"2018","journal-title":"Gene"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"6978303","DOI":"10.1155\/2019\/6978303","article-title":"Induced Pluripotent Stem Cell Derivation and Ex Vivo Gene Correction Using a Mucopolysaccharidosis Type 1 Disease Mouse Model","volume":"2019","author":"Miki","year":"2019","journal-title":"Stem Cells Int."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.jconrel.2018.08.031","article-title":"In vivo genome editing of mucopolysaccharidosis I mice using the CRISPR\/Cas9 system","volume":"288","author":"Schuh","year":"2018","journal-title":"J. Control Release"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/s41434-019-0113-4","article-title":"Neonatal nonviral gene editing with the CRISPR\/Cas9 system improves some cardiovascular, respiratory, and bone disease features of the mucopolysaccharidosis I phenotype in mice","volume":"27","author":"Schuh","year":"2020","journal-title":"Gene Ther."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s40035-022-00314-0","article-title":"CRISPR\/dCas9-Dnmt3a-mediated targeted DNA methylation of APP rescues brain pathology in a mouse model of Alzheimer\u2019s disease","volume":"11","author":"Park","year":"2022","journal-title":"Transl. Neurodegener."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.omtn.2018.03.007","article-title":"CRISPR\/Cas9 Mediated Disruption of the Swedish APP Allele as a Therapeutic Approach for Early-Onset Alzheimer\u2019s Disease","volume":"11","author":"Gyorgy","year":"2018","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Zhang, S., Li, X., Zhang, L., Meng, X., Ma, L., Zhang, G., Wu, H., Liang, L., Cao, M., and Mei, F. (2020). Identification of a Rare PSEN1 Mutation (Thr119Ile) in Late-Onset Alzheimer\u2019s Disease With Early Presentation of Behavioral Disturbance. Front. Psychiatry, 11.","DOI":"10.3389\/fpsyt.2020.00347"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.omtn.2022.03.022","article-title":"CRISPR-Cas9 treatment partially restores amyloid-beta 42\/40 in human fibroblasts with the Alzheimer\u2019s disease PSEN 1 M146L mutation","volume":"28","author":"Konstantinidis","year":"2022","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.omtn.2021.02.032","article-title":"Base editing strategy for insertion of the A673T mutation in the APP gene to prevent the development of AD in vitro","volume":"24","author":"Guyon","year":"2021","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/s41467-018-07971-8","article-title":"CRISPR\/Cas9 editing of APP C-terminus attenuates beta-cleavage and promotes alpha-cleavage","volume":"10","author":"Sun","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"eaaz4564c","DOI":"10.1126\/scitranslmed.aaz4564","article-title":"APOE4 disrupts intracellular lipid homeostasis in human iPSC-derived glia","volume":"13","author":"Sienski","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"e7","DOI":"10.1016\/j.jcyt.2019.04.022","article-title":"ApoE4 allele specific knockout using a synthetic Cas9 variant as a potential gene therapy approach for Alzheimer\u2019s disease","volume":"21","author":"Rabinowitz","year":"2019","journal-title":"Cytotherapy"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1186\/s13287-021-02585-2","article-title":"In vitro genome editing rescues parkinsonism phenotypes in induced pluripotent stem cells-derived dopaminergic neurons carrying LRRK2 p.G2019S mutation","volume":"12","author":"Chang","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1111\/ejn.14286","article-title":"Engineering synucleinopathy-resistant human dopaminergic neurons by CRISPR-mediated deletion of the SNCA gene","volume":"49","author":"Chen","year":"2019","journal-title":"Eur. J. Neurosci."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"e44860","DOI":"10.15252\/embr.201744860","article-title":"Knockdown of the mitochondria-localized protein p13 protects against experimental parkinsonism","volume":"19","author":"Inoue","year":"2018","journal-title":"EMBO Rep."},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Alves, C.R.R., Ha, L.L., Yaworski, R., Lazzarotto, C.R., Christie, K.A., Reilly, A., Beauvais, A., Doll, R.M., de la Cruz, D., and Maguire, C.A. (2023). Base editing as a genetic treatment for spinal muscular atrophy. bioRxiv.","DOI":"10.1101\/2023.01.20.524978"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1093\/nsr\/nwz131","article-title":"Disruption of splicing-regulatory elements using CRISPR\/Cas9 to rescue spinal muscular atrophy in human iPSCs and mice","volume":"7","author":"Li","year":"2020","journal-title":"Natl. Sci. Rev."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1126\/science.aad5143","article-title":"In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy","volume":"351","author":"Nelson","year":"2016","journal-title":"Science"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1126\/science.1254445","article-title":"Prevention of muscular dystrophy in mice by CRISPR\/Cas9-mediated editing of germline DNA","volume":"345","author":"Long","year":"2014","journal-title":"Science"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.omtm.2023.08.009","article-title":"CRISPR-Cas9 homology-independent targeted integration of exons 1-19 restores full-length dystrophin in mice","volume":"30","author":"Stephenson","year":"2023","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"103327","DOI":"10.1016\/j.scr.2024.103327","article-title":"Generation of human induced pluripotent stem cell line derived from Becker muscular dystrophy patient with CRISPR\/Cas9-mediated correction of DMD gene mutation","volume":"76","author":"Przymuszala","year":"2024","journal-title":"Stem Cell Res."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1002\/jcsm.13171","article-title":"The X-linked Becker muscular dystrophy (bmx) mouse models Becker muscular dystrophy via deletion of murine dystrophin exons 45-47","volume":"14","author":"Heier","year":"2023","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"dmm050595","DOI":"10.1242\/dmm.050595","article-title":"Generation and characterization of a novel mouse model of Becker Muscular Dystrophy with a deletion of exons 52 to 55","volume":"18","author":"Perillat","year":"2024","journal-title":"Dis. Models Mech."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.omtn.2019.02.019","article-title":"Allele-Specific CRISPR\/Cas9 Correction of a Heterozygous DNM2 Mutation Rescues Centronuclear Myopathy Cell Phenotypes","volume":"16","author":"Rabai","year":"2019","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"113507","DOI":"10.1016\/j.yexcr.2023.113507","article-title":"ACTA1 H40Y mutant iPSC-derived skeletal myocytes display mitochondrial defects in an in vitro model of nemaline myopathy","volume":"424","author":"Gartz","year":"2023","journal-title":"Exp. Cell Res."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"10321","DOI":"10.1038\/s41598-020-65259-8","article-title":"CRISPR-Cas9 generated Pompe knock-in murine model exhibits early-onset hypertrophic cardiomyopathy and skeletal muscle weakness","volume":"10","author":"Huang","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Rossiaud, L., Fragner, P., Barbon, E., Gardin, A., Benabides, M., Pellier, E., Cosette, J., El Kassar, L., Giraud-Triboult, K., and Nissan, X. (2023). Pathological modeling of glycogen storage disease type III with CRISPR\/Cas9 edited human pluripotent stem cells. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1163427"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"305716","DOI":"10.1155\/2015\/305716","article-title":"Efficient Mitochondrial Genome Editing by CRISPR\/Cas9","volume":"2015","author":"Jo","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_171","first-page":"100329","article-title":"Direct evidence of CRISPR-Cas9-mediated mitochondrial genome editing","volume":"3","author":"Bi","year":"2022","journal-title":"Innovation"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1038\/s41587-020-00781-8","article-title":"Targeting herpes simplex virus with CRISPR-Cas9 cures herpetic stromal keratitis in mice","volume":"39","author":"Yin","year":"2021","journal-title":"Nat. Biotechnol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"3163","DOI":"10.1016\/j.ymthe.2023.08.021","article-title":"In vivo CRISPR gene editing in patients with herpetic stromal keratitis","volume":"31","author":"Wei","year":"2023","journal-title":"Mol. Ther. J. Am. Soc. Gene Ther."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"e0079524","DOI":"10.1128\/mbio.00795-24","article-title":"Targeted eradication of EBV-positive cancer cells by CRISPR\/dCas9-mediated EBV reactivation in combination with ganciclovir","volume":"15","author":"Sugiokto","year":"2024","journal-title":"mBio"},{"key":"ref_175","first-page":"2197","article-title":"CRISPR\/Cas9-mediated cervical cancer treatment targeting human papillomavirus E6","volume":"17","author":"Yoshiba","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"e28144","DOI":"10.1002\/jmv.28144","article-title":"CRISPR\/Cas9-HPV-liposome enhances antitumor immunity and treatment of HPV infection-associated cervical cancer","volume":"95","author":"Zhen","year":"2023","journal-title":"J. Med. Virol."},{"key":"ref_177","unstructured":"ClinicalTrials (2021). A Phase 1\/2a, Sequential Cohort, Single Ascending Dose Study of the Safety, Tolerability, Biodistribution, and Pharmacodynamics of EBT 101 in Aviremic HIV-1 Infected Adults on Stable Antiretroviral Therapy."},{"key":"ref_178","unstructured":"Excision (2026, March 30). Excision BioTherapeutics Presents Positive Interim Clinical Data from Ongoing Phase 1\/2 Trial of EBT-101 for the Treatment of HIV at ESGCT 30th Annual Congress. Available online: https:\/\/www.globenewswire.com\/news-release\/2023\/10\/25\/2766525\/0\/en\/Excision-BioTherapeutics-Presents-Positive-Interim-Clinical-Data-from-Ongoing-Phase-1-2-Trial-of-EBT-101-for-the-Treatment-of-HIV-at-ESGCT-30th-Annual-Congress.html."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.1016\/j.ymthe.2017.04.027","article-title":"CRISPR\/Cas9-Mediated CCR5 Ablation in Human Hematopoietic Stem\/Progenitor Cells Confers HIV-1 Resistance In Vivo","volume":"25","author":"Xu","year":"2017","journal-title":"Mol. Ther. J. Am. Soc. Gene Ther."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"9184","DOI":"10.1002\/jcp.27595","article-title":"Genome-wide CRISPR-Cas9 viability screen reveals genes involved in TNF-alpha-induced apoptosis of human umbilical vein endothelial cells","volume":"234","author":"Cai","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_181","doi-asserted-by":"crossref","unstructured":"Moerke, C., Bleibaum, F., Kunzendorf, U., and Krautwald, S. (2019). Combined Knockout of RIPK3 and MLKL Reveals Unexpected Outcome in Tissue Injury and Inflammation. Front. Cell Dev. Biol., 7.","DOI":"10.3389\/fcell.2019.00019"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.ajpath.2012.11.005","article-title":"A novel function of MUC18: Amplification of lung inflammation during bacterial infection","volume":"182","author":"Wu","year":"2013","journal-title":"Am. J. Pathol."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1038\/gt.2015.53","article-title":"CRISPR-Cas9-mediated gene knockout in primary human airway epithelial cells reveals a proinflammatory role for MUC18","volume":"22","author":"Chu","year":"2015","journal-title":"Gene Ther."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1016\/j.celrep.2015.08.013","article-title":"Modeling Human Severe Combined Immunodeficiency and Correction by CRISPR\/Cas9-Enhanced Gene Targeting","volume":"12","author":"Chang","year":"2015","journal-title":"Cell Rep."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1038\/mt.2013.59","article-title":"HLA engineering of human pluripotent stem cells","volume":"21","author":"Riolobos","year":"2013","journal-title":"Mol. Ther. J. Am. Soc. Gene Ther."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"5697","DOI":"10.1182\/blood-2012-01-405365","article-title":"A foundation for universal T-cell based immunotherapy: T cells engineered to express a CD19-specific chimeric-antigen-receptor and eliminate expression of endogenous TCR","volume":"119","author":"Torikai","year":"2012","journal-title":"Blood"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"1548243","DOI":"10.1080\/2162402X.2018.1548243","article-title":"CIITA-related block of HLA class II expression, upregulation of HLA class I, and heterogeneous expression of immune checkpoints in hepatocarcinomas: Implications for new therapeutic approaches","volume":"8","author":"Ramia","year":"2019","journal-title":"Oncoimmunology"},{"key":"ref_188","unstructured":"ClinicalTrials (2021). Phase I Trial of Programmed Allogeneic CRISPR-Edited T Cells (PACE) Gene Edited to Eliminate Endogenous TCR, HLA-Class I and HLA-Class II and Engineered to Express Anti-CD19 Chimeric Antigen Receptor (PACE CART19) in Patients with Relapsed Or Refractory CD19+ Leukemia and Lymphoma."},{"key":"ref_189","unstructured":"(2019). A Phase 1\/2 Dose Escalation and Cohort Expansion Study of the Safety and Efficacy of Allogeneic CRISPR-Cas9-Engineered T Cells (CTX110) in Subjects with Relapsed or Refractory B-Cell Malignancies (CARBON), ClinicalTrials."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/S1470-2045(24)00508-4","article-title":"Safety and activity of CTX130, a CD70-targeted allogeneic CRISPR-Cas9-engineered CAR T-cell therapy, in patients with relapsed or refractory T-cell malignancies (COBALT-LYM): A single-arm, open-label, phase 1, dose-escalation study","volume":"26","author":"Iyer","year":"2025","journal-title":"Lancet. Oncol."},{"key":"ref_191","unstructured":"U.S. Food and Drug Administration (2026, March 30). FDA Approves Axicabtagene Ciloleucel for Large B-Cell Lymphoma, Available online: https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-axicabtagene-ciloleucel-large-b-cell-lymphoma."},{"key":"ref_192","unstructured":"U.S. Food and Drug Administration (2026, March 08). Approved Cellular and Gene Therapy Products, Available online: https:\/\/www.fda.gov\/vaccines-blood-biologics\/cellular-gene-therapy-products\/approved-cellular-and-gene-therapy-products."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/s41467-024-44786-2","article-title":"Generation and optimization of off-the-shelf immunotherapeutics targeting TCR-Vbeta2+ T cell malignancy","volume":"15","author":"Ren","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_194","unstructured":"U.S. Food and Drug Administration (2026, March 08). In Vitro Companion Diagnostic Devices: Guidance for Industry and FDA Staff, Available online: https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/in-vitro-companion-diagnostic-devices."},{"key":"ref_195","unstructured":"European Union (2026, March 08). Regulation (EU) 2017\/746 of the European Parliament and of the Council of 5 April 2017 on In Vitro Diagnostic Medical Devices and Repealing Directive 98\/79\/EC and Commission Decision 2010\/227\/EU, Available online: https:\/\/eur-lex.europa.eu\/eli\/reg\/2017\/746\/oj\/eng."},{"key":"ref_196","unstructured":"U.S. Food and Drug Administration (2026, March 08). Long Term Follow-Up After Administration of Human Gene Therapy Products, Available online: https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/long-term-follow-after-administration-human-gene-therapy-products."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"2433","DOI":"10.1016\/j.ymthe.2024.07.001","article-title":"In vivo genome editing for inherited retinal disease: Opportunities and challenges","volume":"32","author":"Collin","year":"2024","journal-title":"Mol. Ther. J. Am. Soc. Gene Ther."},{"key":"ref_198","unstructured":"CRISPR Medicine (2021). CAST-Seq: A New and Much-Needed Tool for Assessing the Safety of Designer Nucleases, CRISPR Medicine. Available online: https:\/\/crisprmedicinenews.com\/news\/cast-seq-a-new-and-much-needed-tool-for-assessing-the-safety-of-designer-nucleases\/."},{"key":"ref_199","doi-asserted-by":"crossref","unstructured":"Giannoukos, G., Ciulla, D.M., Marco, E., Abdulkerim, H.S., Barrera, L.A., Bothmer, A., Dhanapal, V., Gloskowski, S.W., Jayaram, H., and Maeder, M.L. (2018). UDiTaS, a genome editing detection method for indels and genome rearrangements. BMC Genom., 19.","DOI":"10.1186\/s12864-018-4561-9"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1038\/s41467-022-28244-5","article-title":"CRISPR-Cas9 induces large structural variants at on-target and off-target sites in vivo that segregate across generations","volume":"13","author":"Hoijer","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/nbt.3117","article-title":"GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases","volume":"33","author":"Tsai","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/nmeth.4278","article-title":"CIRCLE-seq: A highly sensitive in vitro screen for genome-wide CRISPR-Cas9 nuclease off-targets","volume":"14","author":"Tsai","year":"2017","journal-title":"Nat. Methods"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1038\/s41587-020-0555-7","article-title":"CHANGE-seq reveals genetic and epigenetic effects on CRISPR-Cas9 genome-wide activity","volume":"38","author":"Lazzarotto","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"D914","DOI":"10.1093\/nar\/gkae1025","article-title":"CRISPRoffT: Comprehensive database of CRISPR\/Cas off-targets","volume":"53","author":"Wang","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1038\/nbt.4192","article-title":"Repair of double-strand breaks induced by CRISPR-Cas9 leads to large deletions and complex rearrangements","volume":"36","author":"Kosicki","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1038\/s41587-023-02024-y","article-title":"Detection of mosaic and population-level structural variants with Sniffles2","volume":"42","author":"Smolka","year":"2024","journal-title":"Nat. Biotechnol."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"2907","DOI":"10.1093\/bioinformatics\/btz041","article-title":"SVIM: Structural variant identification using mapped long reads","volume":"35","author":"Heller","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1186\/s13059-020-02107-y","article-title":"Long-read-based human genomic structural variation detection with cuteSV","volume":"21","author":"Jiang","year":"2020","journal-title":"Genome Biol."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"3175","DOI":"10.1038\/s41591-023-02636-6","article-title":"Clonal selection of hematopoietic stem cells after gene therapy for sickle cell disease","volume":"29","author":"Cull","year":"2023","journal-title":"Nat. Med."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.bbmt.2018.12.758","article-title":"ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells","volume":"25","author":"Lee","year":"2019","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1038\/s41586-025-09507-9","article-title":"Systematic discovery of CRISPR-boosted CAR T cell immunotherapies","volume":"646","author":"Datlinger","year":"2025","journal-title":"Nature"},{"key":"ref_212","unstructured":"Stansfield, N. (2025). Intellia Puts Phase 3 Trials for Transthyretin Amyloidosis Gene Editing Therapy Nex-Z on Hold Following Grade 4 Liver AE, CGTlive. Available online: https:\/\/www.cgtlive.com\/view\/intellia-phase-3-trials-transthyretin-amyloidosis-gene-editing-therapy-nex-z-hold-grade-4-liver-ae."},{"key":"ref_213","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_214","unstructured":"International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (2023). Nonclinical Biodistribution Considerations for Gene Therapy Products S12, International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. Available online: https:\/\/database.ich.org\/sites\/default\/files\/ICH_S12_Step4_Guideline_2023_0314.pdf."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1038\/s41588-021-00838-7","article-title":"Chromothripsis as an on-target consequence of CRISPR-Cas9 genome editing","volume":"53","author":"Leibowitz","year":"2021","journal-title":"Nat. Genet."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1016\/j.stem.2021.02.002","article-title":"Quantitative evaluation of chromosomal rearrangements in gene-edited human stem cells by CAST-Seq","volume":"28","author":"Turchiano","year":"2021","journal-title":"Cell Stem Cell"},{"key":"ref_217","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."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/7\/644\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T04:29:33Z","timestamp":1775276973000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/7\/644"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,2]]},"references-count":217,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["cells15070644"],"URL":"https:\/\/doi.org\/10.3390\/cells15070644","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,2]]}}}