{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:22:52Z","timestamp":1785410572443,"version":"3.56.0"},"reference-count":250,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"crossref","award":["R01 MH110360"],"award-info":[{"award-number":["R01 MH110360"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"crossref"}]},{"award":["R01 MH110360"],"award-info":[{"award-number":["R01 MH110360"]}],"id":[{"id":"https:\/\/ror.org\/04xeg9z08","id-type":"ROR","asserted-by":"publisher"}]},{"name":"NIMH Comprehensive NeuroHIV Center","award":["P30 MH092177"],"award-info":[{"award-number":["P30 MH092177"]}]},{"name":"Ruth L. Kirschstein National Research Service Award","award":["T32 MH079785"],"award-info":[{"award-number":["T32 MH079785"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Over a decade of advances in Clustered Regularly Interspersed Short Palindromic Repeats (CRISPR) and CRISPR-associated protein 9 (Cas9)-based technologies have culminated in the first-ever FDA-approved CRISPR\/Cas-based therapy. Aside from this approved therapy for sickle cell anemia, several CRISPR\/Cas-based therapies are currently under development or testing for a range of chronic diseases, including viral diseases like human immunodeficiency virus type 1 (HIV-1) infection, genetic diseases like familial hypercholesterolemia, and cancer. The success of these therapies hinges on the effective delivery of CRISPR\/Cas9 components to target regions, efficient Cas endonuclease editing, repair profiles generated, and their resulting outcomes. Here, we discuss the factors that influence the generation of CRISPR\/Cas9-generated repair edits, the overall profiles, and outcome prediction(s), as well as the analytical tools that have been developed to date. Finally, how this technology has been used towards a functional HIV-1 cure is discussed.<\/jats:p>","DOI":"10.3390\/ijms27135905","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:50:37Z","timestamp":1782867037000},"page":"5905","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CRISPR\/Cas9-Based Genome Editing: Understanding Differences in DNA Repair Pathways, Profiles, and Outcomes"],"prefix":"10.3390","volume":"27","author":[{"given":"Samuel N.","family":"Effah","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19102, USA"},{"name":"Center for Molecular Virology and Gene Therapy, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirley C.","family":"Barrera","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19102, USA"},{"name":"Center for Molecular Virology and Gene Therapy, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahia","family":"Urturi Ortiz","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19102, USA"},{"name":"Center for Molecular Virology and Gene Therapy, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Will","family":"Dampier","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19102, USA"},{"name":"Center for Molecular Virology and Gene Therapy, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Nonnemacher","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19102, USA"},{"name":"Center for Molecular Virology and Gene Therapy, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USA"},{"name":"Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5211-0936","authenticated-orcid":false,"given":"Brian","family":"Wigdahl","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19102, USA"},{"name":"Center for Molecular Virology and Gene Therapy, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USA"},{"name":"Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"12133","DOI":"10.1007\/s11033-022-07880-6","article-title":"CRISPR\/Cas9 system: A reliable and facile genome editing tool in modern biology","volume":"49","author":"Javaid","year":"2022","journal-title":"Mol. Biol. Rep."},{"key":"ref_2","first-page":"353","article-title":"Mechanism and Applications of CRISPR\/Cas-9-Mediated Genome Editing","volume":"15","author":"Asmamaw","year":"2021","journal-title":"Biologics"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Uddin, F., Rudin, C.M., and Sen, T. (2020). CRISPR Gene Therapy: Applications, Limitations, and Implications for the Future. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.01387"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Chechik, L., Martin, O., and Soutoglou, E. (2020). Genome Editing Fidelity in the Context of DNA Sequence and Chromatin Structure. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.00319"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Allen, A.G., Chung, C.H., Atkins, A., Dampier, W., Khalili, K., Nonnemacher, M.R., and Wigdahl, B. (2018). Gene Editing of HIV-1 Co-receptors to Prevent and\/or Cure Virus Infection. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.02940"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s12943-023-01925-5","article-title":"Comprehensive review of CRISPR-based gene editing: Mechanisms, challenges, and applications in cancer therapy","volume":"23","author":"Chehelgerdi","year":"2024","journal-title":"Mol. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1126\/science.aat5011","article-title":"CRISPR-Cas guides the future of genetic engineering","volume":"361","author":"Knott","year":"2018","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.tig.2021.02.008","article-title":"DNA Repair Pathway Choices in CRISPR-Cas9-Mediated Genome Editing","volume":"37","author":"Xue","year":"2021","journal-title":"Trends Genet."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Dampier, W., Berman, R., Nonnemacher, M.R., and Wigdahl, B. (2023). Computational analysis of cas proteins unlocks new potential in HIV-1 targeted gene therapy. Front. Genome Ed., 5.","DOI":"10.3389\/fgeed.2023.1248982"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1097\/COH.0000000000000846","article-title":"What\u2019s in a cure: Designing a broad-spectrum HIV gene therapy","volume":"19","author":"Berman","year":"2024","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/s41392-023-01309-7","article-title":"CRISPR\/Cas9 therapeutics: Progress and prospects","volume":"8","author":"Li","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s12033-022-00567-0","article-title":"A Review on the Mechanism and Applications of CRISPR\/Cas9\/Cas12\/Cas13\/Cas14 Proteins Utilized for Genome Engineering","volume":"65","author":"Hillary","year":"2023","journal-title":"Mol. Biotechnol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1093\/pcmedi\/pbab014","article-title":"Applications and challenges of CRISPR-Cas gene-editing to disease treatment in clinics","volume":"4","author":"Liu","year":"2021","journal-title":"Precis. Clin. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5527","DOI":"10.1093\/nar\/gkaa226","article-title":"Extinction of all infectious HIV in cell culture by the CRISPR-Cas12a system with only a single crRNA","volume":"48","author":"Gao","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_15","first-page":"1","article-title":"Challenges and Opportunities in the Application of CRISPR-Cas9: A Review on Genomic Editing and Therapeutic Potentials","volume":"35","author":"Karimi","year":"2026","journal-title":"Med. Princ. Pract."},{"key":"ref_16","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_17","doi-asserted-by":"crossref","unstructured":"Naeem, M., Majeed, S., Hoque, M.Z., and Ahmad, I. (2020). Latest Developed Strategies to Minimize the Off-Target Effects in CRISPR-Cas-Mediated Genome Editing. Cells, 9.","DOI":"10.3390\/cells9071608"},{"key":"ref_18","first-page":"21","article-title":"Recent Advancements in Reducing the Off-Target Effect of CRISPR-Cas9 Genome Editing","volume":"18","author":"Teshome","year":"2024","journal-title":"Biologics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4555","DOI":"10.1097\/MS9.0000000000002146","article-title":"Revolutionary breakthrough: FDA approves CASGEVY, the first CRISPR\/Cas9 gene therapy for sickle cell disease","volume":"86","author":"Singh","year":"2024","journal-title":"Ann. Med. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/s41569-021-00669-3","article-title":"The use of new CRISPR tools in cardiovascular research and medicine","volume":"19","author":"Nishiga","year":"2022","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s40484-014-0030-x","article-title":"Target specificity of the CRISPR-Cas9 system","volume":"2","author":"Wu","year":"2014","journal-title":"Quant. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1089\/aid.2017.0274","article-title":"Broad-Spectrum and Personalized Guide RNAs for CRISPR\/Cas9 HIV-1 Therapeutics","volume":"34","author":"Dampier","year":"2018","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.amjmed.2023.12.018","article-title":"CRISPR Therapy of Sickle Cell Disease: The Dawning of the Gene Editing Era","volume":"137","author":"Adashi","year":"2024","journal-title":"Am. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Gurrola, T.E., Effah, S.N., Sariyer, I.K., Dampier, W., Nonnemacher, M.R., and Wigdahl, B. (2024). Delivering CRISPR to the HIV-1 reservoirs. Front. Microbiol., 15.","DOI":"10.3389\/fmicb.2024.1393974"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"eadd8643","DOI":"10.1126\/science.add8643","article-title":"CRISPR technology: A decade of genome editing is only the beginning","volume":"379","author":"Wang","year":"2023","journal-title":"Science"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Shumega, A.R., Pavlov, Y.I., Chirinskaite, A.V., Rubel, A.A., Inge-Vechtomov, S.G., and Stepchenkova, E.I. (2024). CRISPR\/Cas9 as a Mutagenic Factor. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25020823"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.1038\/s41467-019-10366-y","article-title":"Sequential LASER ART and CRISPR Treatments Eliminate HIV-1 in a Subset of Infected Humanized Mice","volume":"10","author":"Dash","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6065","DOI":"10.1038\/s41467-020-19821-7","article-title":"CRISPR based editing of SIV proviral DNA in ART treated non-human primates","volume":"11","author":"Mancuso","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"8417","DOI":"10.1093\/nar\/gky653","article-title":"Decoding non-random mutational signatures at Cas9 targeted sites","volume":"46","author":"Taylor","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/nbt.4317","article-title":"Predicting the mutations generated by repair of Cas9-induced double-strand breaks","volume":"37","author":"Allen","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1038\/s41587-019-0203-2","article-title":"Large dataset enables prediction of repair after CRISPR-Cas9 editing in primary T cells","volume":"37","author":"Leenay","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7989","DOI":"10.1093\/nar\/gkz487","article-title":"Massively parallel profiling and predictive modeling of the outcomes of CRISPR\/Cas9-mediated double-strand break repair","volume":"47","author":"Chen","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/j.molcel.2018.11.031","article-title":"Target-Specific Precision of CRISPR-Mediated Genome Editing","volume":"73","author":"Chakrabarti","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1038\/s41586-018-0686-x","article-title":"Predictable and precise template-free CRISPR editing of pathogenic variants","volume":"563","author":"Shen","year":"2018","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/s41421-019-0088-8","article-title":"Optimizing genome editing strategy by primer-extension-mediated sequencing","volume":"5","author":"Yin","year":"2019","journal-title":"Cell Discov."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8732","DOI":"10.1093\/nar\/gkab686","article-title":"Global detection of DNA repair outcomes induced by CRISPR-Cas9","volume":"49","author":"Liu","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1016\/j.csbj.2020.06.026","article-title":"CRISPR-sub: Analysis of DNA substitution mutations caused by CRISPR-Cas9 in human cells","volume":"18","author":"Hwang","year":"2020","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"10271","DOI":"10.1038\/s41467-024-54566-7","article-title":"The interplay of DNA repair context with target sequence predictably biases Cas9-generated mutations","volume":"15","author":"Pallaseni","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3422","DOI":"10.1038\/s41467-022-30480-8","article-title":"Cas9-induced large deletions and small indels are controlled in a convergent fashion","volume":"13","author":"Kosicki","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1089\/crispr.2020.0022","article-title":"Deconvolution of Complex DNA Repair (DECODR): Establishing a Novel Deconvolution Algorithm for Comprehensive Analysis of CRISPR-Edited Sanger Sequencing Data","volume":"4","author":"Bloh","year":"2021","journal-title":"Cris. J."},{"key":"ref_41","first-page":"e1269","article-title":"A simple and highly efficient method for multi-allelic CRISPR-Cas9 editing in primary cell cultures","volume":"3","author":"Hoellerbauer","year":"2020","journal-title":"Cancer Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.omtn.2021.03.005","article-title":"Efficient correction of Duchenne muscular dystrophy mutations by SpCas9 and dual gRNAs","volume":"24","author":"Xiang","year":"2021","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Binda, C.S., Klaver, B., Berkhout, B., and Das, A.T. (2020). CRISPR-Cas9 Dual-gRNA Attack Causes Mutation, Excision and Inversion of the HIV-1 Proviral DNA. Viruses, 12.","DOI":"10.3390\/v12030330"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2819","DOI":"10.1016\/j.celrep.2016.11.057","article-title":"A Combinatorial CRISPR-Cas9 Attack on HIV-1 DNA Extinguishes All Infectious Provirus in Infected T Cell Cultures","volume":"17","author":"Wang","year":"2016","journal-title":"Cell Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-12-394300-2.00001-6","article-title":"Classical and alternative end-joining pathways for repair of lymphocyte-specific and general DNA double-strand breaks","volume":"116","author":"Boboila","year":"2012","journal-title":"Adv. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1146\/annurev.biochem.052308.093131","article-title":"The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway","volume":"79","author":"Lieber","year":"2010","journal-title":"Annu. Rev. Biochem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.tibs.2015.08.006","article-title":"Microhomology-Mediated End Joining: A Back-up Survival Mechanism or Dedicated Pathway?","volume":"40","author":"Sfeir","year":"2015","journal-title":"Trends Biochem. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1074\/jbc.R700039200","article-title":"The mechanism of human nonhomologous DNA end joining","volume":"283","author":"Lieber","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/j.dnarep.2004.06.001","article-title":"The cellular response to general and programmed DNA double strand breaks","volume":"3","author":"Bassing","year":"2004","journal-title":"DNA Repair"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"55117","DOI":"10.1074\/jbc.M404524200","article-title":"Involvement of poly(ADP-ribose) polymerase-1 and XRCC1\/DNA ligase III in an alternative route for DNA double-strand breaks rejoining","volume":"279","author":"Audebert","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.omtm.2021.03.024","article-title":"CRISPAltRations: A validated cloud-based approach for interrogation of double-strand break repair mediated by CRISPR genome editing","volume":"21","author":"Kurgan","year":"2021","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Fattah, F., Lee, E.H., Weisensel, N., Wang, Y., Lichter, N., and Hendrickson, E.A. (2010). Ku regulates the non-homologous end joining pathway choice of DNA double-strand break repair in human somatic cells. PLoS Genet., 6.","DOI":"10.1371\/journal.pgen.1000855"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"5333","DOI":"10.1093\/nar\/26.23.5333","article-title":"Double-strand break repair in Ku86- and XRCC4-deficient cells","volume":"26","author":"Kabotyanski","year":"1998","journal-title":"Nucleic Acids Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5377","DOI":"10.1093\/nar\/gkg728","article-title":"Biochemical evidence for Ku-independent backup pathways of NHEJ","volume":"31","author":"Wang","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4639","DOI":"10.1093\/nar\/24.23.4639","article-title":"Identification of a Saccharomyces cerevisiae Ku80 homologue: Roles in DNA double strand break rejoining and in telomeric maintenance","volume":"24","author":"Boulton","year":"1996","journal-title":"Nucleic Acids Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1038\/nature06020","article-title":"IgH class switching and translocations use a robust non-classical end-joining pathway","volume":"449","author":"Yan","year":"2007","journal-title":"Nature"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1084\/jem.20092449","article-title":"Alternative end-joining catalyzes class switch recombination in the absence of both Ku70 and DNA ligase 4","volume":"207","author":"Boboila","year":"2010","journal-title":"J. Exp. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"8820","DOI":"10.1128\/MCB.23.23.8820-8828.2003","article-title":"Yeast Mre11 and Rad1 proteins define a Ku-independent mechanism to repair double-strand breaks lacking overlapping end sequences","volume":"23","author":"Ma","year":"2003","journal-title":"Mol. Cell Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1002\/1521-4141(200203)32:3<701::AID-IMMU701>3.0.CO;2-T","article-title":"Different types of V(D)J recombination and end-joining defects in DNA double-strand break repair mutant mammalian cells","volume":"32","author":"Verkaik","year":"2002","journal-title":"Eur. J. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3034","DOI":"10.1073\/pnas.0915067107","article-title":"Alternative end-joining catalyzes robust IgH locus deletions and translocations in the combined absence of ligase 4 and Ku70","volume":"107","author":"Boboila","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.dnarep.2014.02.006","article-title":"Non-homologous end joining often uses microhomology: Implications for alternative end joining","volume":"17","author":"Pannunzio","year":"2014","journal-title":"DNA Repair"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/cr.2007.108","article-title":"Flexibility in the order of action and in the enzymology of the nuclease, polymerases, and ligase of vertebrate non-homologous DNA end joining: Relevance to cancer, aging, and the immune system","volume":"18","author":"Lieber","year":"2008","journal-title":"Cell Res."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Kieffer, S.R., and Lowndes, N.F. (2022). Immediate-Early, Early, and Late Responses to DNA Double Stranded Breaks. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.793884"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Betermier, M., Bertrand, P., and Lopez, B.S. (2014). Is non-homologous end-joining really an inherently error-prone process?. PLoS Genet., 10.","DOI":"10.1371\/journal.pgen.1004086"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.molcel.2018.04.016","article-title":"Kinetics and Fidelity of the Repair of Cas9-Induced Double-Strand DNA Breaks","volume":"70","author":"Brinkman","year":"2018","journal-title":"Mol. Cell"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1084\/jem.20081623","article-title":"Altered kinetics of nonhomologous end joining and class switch recombination in ligase IV-deficient B cells","volume":"205","author":"Han","year":"2008","journal-title":"J. Exp. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"6233","DOI":"10.1038\/ncomms7233","article-title":"Interactome analysis identifies a new paralogue of XRCC4 in non-homologous end joining DNA repair pathway","volume":"6","author":"Xing","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2561","DOI":"10.1093\/nar\/gkn094","article-title":"Distinct roles of XRCC4 and Ku80 in non-homologous end-joining of endonuclease- and ionizing radiation-induced DNA double-strand breaks","volume":"36","author":"Schliecker","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1093\/emboj\/17.2.609","article-title":"Ku protein stimulates DNA end joining by mammalian DNA ligases: A direct role for Ku in repair of DNA double-strand breaks","volume":"17","author":"Ramsden","year":"1998","journal-title":"EMBO J."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1093\/nar\/29.8.1653","article-title":"Genetic evidence for the involvement of DNA ligase IV in the DNA-PK-dependent pathway of non-homologous end joining in mammalian cells","volume":"29","author":"Wang","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"29030","DOI":"10.1074\/jbc.M505277200","article-title":"DNA joint dependence of pol X family polymerase action in nonhomologous end joining","volume":"280","author":"Daley","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"582","DOI":"10.18632\/aging.100197","article-title":"ATM-independent, high-fidelity nonhomologous end joining predominates in human embryonic stem cells","volume":"2","author":"Adams","year":"2010","journal-title":"Aging"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"20190966","DOI":"10.1259\/bjr.20190966","article-title":"Canonical DNA non-homologous end-joining; capacity versus fidelity","volume":"93","author":"Shibata","year":"2020","journal-title":"Br. J. Radiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1186\/s13059-018-1518-x","article-title":"Harnessing accurate non-homologous end joining for efficient precise deletion in CRISPR\/Cas9-mediated genome editing","volume":"19","author":"Guo","year":"2018","journal-title":"Genome Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"13049","DOI":"10.1038\/ncomms13049","article-title":"Classical non-homologous end-joining pathway utilizes nascent RNA for error-free double-strand break repair of transcribed genes","volume":"7","author":"Chakraborty","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1093\/nar\/gkaa1205","article-title":"A pathway for error-free non-homologous end joining of resected meiotic double-strand breaks","volume":"49","author":"Hatkevich","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1038\/ncb1624","article-title":"Formation of NHEJ-derived reciprocal chromosomal translocations does not require Ku70","volume":"9","author":"Weinstock","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"5249","DOI":"10.1093\/nar\/gkh842","article-title":"DNA double strand break repair in human bladder cancer is error prone and involves microhomology-associated end-joining","volume":"32","author":"Bentley","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1016\/j.dnarep.2013.10.005","article-title":"The absence of Ku but not defects in classical non-homologous end-joining is required to trigger PARP1-dependent end-joining","volume":"12","author":"Mansour","year":"2013","journal-title":"DNA Repair"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"13785","DOI":"10.1038\/ncomms13785","article-title":"WRN regulates pathway choice between classical and alternative non-homologous end joining","volume":"7","author":"Shamanna","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"6630","DOI":"10.1073\/pnas.110152897","article-title":"The nonhomologous end-joining pathway of DNA repair is required for genomic stability and the suppression of translocations","volume":"97","author":"Ferguson","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/nsmb.1940","article-title":"An essential role for CtIP in chromosomal translocation formation through an alternative end-joining pathway","volume":"18","author":"Zhang","year":"2011","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Jiang, Y. (2022). Contribution of Microhomology to Genome Instability: Connection between DNA Repair and Replication Stress. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232112937"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/nsmb.1942","article-title":"CtIP promotes microhomology-mediated alternative end joining during class-switch recombination","volume":"18","author":"Matthews","year":"2011","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1038\/nature06168","article-title":"Rag mutations reveal robust alternative end joining","volume":"449","author":"Corneo","year":"2007","journal-title":"Nature"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.tig.2008.08.007","article-title":"MMEJ repair of double-strand breaks (director\u2019s cut): Deleted sequences and alternative endings","volume":"24","author":"McVey","year":"2008","journal-title":"Trends Genet."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Simsek, D., Brunet, E., Wong, S.Y., Katyal, S., Gao, Y., McKinnon, P.J., Lou, J., Zhang, L., Li, J., and Rebar, E.J. (2011). DNA ligase III promotes alternative nonhomologous end-joining during chromosomal translocation formation. PLoS Genet., 7.","DOI":"10.1371\/journal.pgen.1002080"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"5706","DOI":"10.1093\/nar\/gkq379","article-title":"Synthesis-dependent microhomology-mediated end joining accounts for multiple types of repair junctions","volume":"38","author":"Yu","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"7720","DOI":"10.1073\/pnas.1213431110","article-title":"Microhomology-mediated End Joining and Homologous Recombination share the initial end resection step to repair DNA double-strand breaks in mammalian cells","volume":"110","author":"Truong","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e1697","DOI":"10.1038\/cddis.2015.58","article-title":"Homology and enzymatic requirements of microhomology-dependent alternative end joining","volume":"6","author":"Sharma","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Decottignies, A. (2013). Alternative end-joining mechanisms: A historical perspective. Front. Genet., 4.","DOI":"10.3389\/fgene.2013.00048"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"3297","DOI":"10.1093\/nar\/gkn184","article-title":"Human DNA ligases I and III, but not ligase IV, are required for microhomology-mediated end joining of DNA double-strand breaks","volume":"36","author":"Liang","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Bennardo, N., Cheng, A., Huang, N., and Stark, J.M. (2008). Alternative-NHEJ is a mechanistically distinct pathway of mammalian chromosome break repair. PLoS Genet., 4.","DOI":"10.1371\/journal.pgen.1000110"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2484","DOI":"10.1038\/s41467-018-04867-5","article-title":"C-NHEJ without indels is robust and requires synergistic function of distinct XLF domains","volume":"9","author":"Bhargava","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"4020","DOI":"10.1158\/0008-5472.CAN-04-3055","article-title":"DNA ligase III as a candidate component of backup pathways of nonhomologous end joining","volume":"65","author":"Wang","year":"2005","journal-title":"Cancer Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"6065","DOI":"10.1093\/nar\/gkq387","article-title":"The alternative end-joining pathway for repair of DNA double-strand breaks requires PARP1 but is not dependent upon microhomologies","volume":"38","author":"Mansour","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2866","DOI":"10.4161\/cc.9.14.12363","article-title":"ATM regulates Mre11-dependent DNA end-degradation and microhomology-mediated end joining","volume":"9","author":"Rahal","year":"2010","journal-title":"Cell Cycle"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.molcel.2016.06.020","article-title":"Essential Roles for Polymerase theta-Mediated End Joining in the Repair of Chromosome Breaks","volume":"63","author":"Wyatt","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"11077","DOI":"10.1038\/s41467-025-67243-0","article-title":"Repurposing clinically safe drugs for DNA repair pathway choice in CRISPR genome editing and synthetic lethality","volume":"16","author":"Macak","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1177\/1947601910383418","article-title":"Upregulation of Poly (ADP-Ribose) Polymerase-1 (PARP1) in Triple-Negative Breast Cancer and Other Primary Human Tumor Types","volume":"1","author":"Ossovskaya","year":"2010","journal-title":"Genes Cancer"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.molcel.2016.06.037","article-title":"DNA Repair Profiling Reveals Nonrandom Outcomes at Cas9-Mediated Breaks","volume":"63","author":"Capurso","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1126\/science.1246981","article-title":"Genetic screens in human cells using the CRISPR-Cas9 system","volume":"343","author":"Wang","year":"2014","journal-title":"Science"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2216","DOI":"10.1016\/j.molcel.2021.03.032","article-title":"Impact of chromatin context on Cas9-induced DNA double-strand break repair pathway balance","volume":"81","author":"Schep","year":"2021","journal-title":"Mol. Cell"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/978-981-13-0593-1_2","article-title":"Induction of Chromosomal Translocations with CRISPR-Cas9 and Other Nucleases: Understanding the Repair Mechanisms That Give Rise to Translocations","volume":"1044","author":"Brunet","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"van Diemen, F.R., Kruse, E.M., Hooykaas, M.J., Bruggeling, C.E., Schurch, A.C., van Ham, P.M., Imhof, S.M., Nijhuis, M., Wiertz, E.J., and Lebbink, R.J. (2016). CRISPR\/Cas9-Mediated Genome Editing of Herpesviruses Limits Productive and Latent Infections. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005701"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1093\/jmcb\/mjv016","article-title":"Efficient inversions and duplications of mammalian regulatory DNA elements and gene clusters by CRISPR\/Cas9","volume":"7","author":"Li","year":"2015","journal-title":"J. Mol. Cell Biol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"4056","DOI":"10.1038\/s41467-019-12028-5","article-title":"CRISPR-Cas9-based mutagenesis frequently provokes on-target mRNA misregulation","volume":"10","author":"Tuladhar","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1002\/jrsm.1456","article-title":"Commentary to Gusenbauer and Haddaway 2020: Evaluating retrieval qualities of Google Scholar and PubMed","volume":"12","author":"Klopfenstein","year":"2021","journal-title":"Res. Synth. Methods"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Hutchins, B.I., Baker, K.L., Davis, M.T., Diwersy, M.A., Haque, E., Harriman, R.M., Hoppe, T.A., Leicht, S.A., Meyer, P., and Santangelo, G.M. (2019). The NIH Open Citation Collection: A public access, broad coverage resource. PLoS Biol., 17.","DOI":"10.1371\/journal.pbio.3000385"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.3390\/cells11111847","article-title":"Predicting CRISPR\/Cas9 Repair Outcomes by Attention-Based Deep Learning Framework","volume":"11","author":"Liu","year":"2022","journal-title":"Cells"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"i342","DOI":"10.1093\/bioinformatics\/btab268","article-title":"CROTON: An automated and variant-aware deep learning framework for predicting CRISPR\/Cas9 editing outcomes","volume":"37","author":"Li","year":"2021","journal-title":"Bioinformatics"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"gkaf105","DOI":"10.1093\/nar\/gkaf105","article-title":"Packaged delivery of CRISPR-Cas9 ribonucleoproteins accelerates genome editing","volume":"53","author":"Karp","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1101\/gr.171322.113","article-title":"Highly efficient RNA-guided genome editing in human cells via delivery of purified Cas9 ribonucleoproteins","volume":"24","author":"Kim","year":"2014","journal-title":"Genome Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"E2040","DOI":"10.1073\/pnas.1716855115","article-title":"CRISPR\/Cas9 cleavages in budding yeast reveal templated insertions and strand-specific insertion\/deletion profiles","volume":"115","author":"Lemos","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1038\/s41587-024-02238-8","article-title":"Linking CRISPR-Cas9 double-strand break profiles to gene editing precision with BreakTag","volume":"43","author":"Longo","year":"2025","journal-title":"Nat. Biotechnol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1146\/annurev-genet-110711-155540","article-title":"Modernizing the nonhomologous end-joining repertoire: Alternative and classical NHEJ share the stage","volume":"47","author":"Deriano","year":"2013","journal-title":"Annu. Rev. Genet."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/nrm.2017.48","article-title":"Non-homologous DNA end joining and alternative pathways to double-strand break repair","volume":"18","author":"Chang","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.omtn.2018.03.010","article-title":"Development of a Reporter System to Explore MMEJ in the Context of Replacing Large Genomic Fragments","volume":"11","author":"Yanik","year":"2018","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"8815","DOI":"10.1093\/nar\/gkae570","article-title":"Chromatin context-dependent effects of epigenetic drugs on CRISPR-Cas9 editing","volume":"52","author":"Schep","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"5334","DOI":"10.1038\/s41467-024-49232-x","article-title":"Widespread chromatin context-dependencies of DNA double-strand break repair proteins","volume":"15","author":"Vergara","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1093\/plphys\/kiac285","article-title":"Epigenetic features drastically impact CRISPR-Cas9 efficacy in plants","volume":"190","author":"Weiss","year":"2022","journal-title":"Plant Physiol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"5775","DOI":"10.1038\/s41467-020-19502-5","article-title":"CHD7 and 53BP1 regulate distinct pathways for the re-ligation of DNA double-strand breaks","volume":"11","author":"Rother","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1667\/RR13572.1","article-title":"Role of 53BP1 in the regulation of DNA double-strand break repair pathway choice","volume":"181","author":"Gupta","year":"2014","journal-title":"Radiat. Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"15019","DOI":"10.1038\/celldisc.2015.19","article-title":"Cell cycle-dependent inhibition of 53BP1 signaling by BRCA1","volume":"1","author":"Feng","year":"2015","journal-title":"Cell Discov."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"15751","DOI":"10.1038\/s41598-019-52078-9","article-title":"Genome-scale CRISPR screens are efficient in non-homologous end-joining deficient cells","volume":"9","author":"Salic","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"4856","DOI":"10.1038\/s41467-019-12829-8","article-title":"Genome-wide microhomologies enable precise template-free editing of biologically relevant deletion mutations","volume":"10","author":"Grajcarek","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"9558","DOI":"10.1074\/jbc.M808906200","article-title":"Human CtIP mediates cell cycle control of DNA end resection and double strand break repair","volume":"284","author":"Huertas","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/nature07215","article-title":"CDK targets Sae2 to control DNA-end resection and homologous recombination","volume":"455","author":"Huertas","year":"2008","journal-title":"Nature"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.molcel.2007.09.009","article-title":"Ctp1 is a cell-cycle-regulated protein that functions with Mre11 complex to control double-strand break repair by homologous recombination","volume":"28","author":"Limbo","year":"2007","journal-title":"Mol. Cell"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1083\/jcb.201103103","article-title":"Cdk1 uncouples CtIP-dependent resection and Rad51 filament formation during M-phase double-strand break repair","volume":"194","author":"Peterson","year":"2011","journal-title":"J. Cell Biol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"9883","DOI":"10.1038\/s41467-025-66058-3","article-title":"Characterizing and controlling CRISPR repair outcomes in nondividing human cells","volume":"16","author":"Ramadoss","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1021\/acssynbio.5b00299","article-title":"The Impact of Chromatin Dynamics on Cas9-Mediated Genome Editing in Human Cells","volume":"6","author":"Daer","year":"2017","journal-title":"ACS Synth. Biol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"e13450","DOI":"10.7554\/eLife.13450","article-title":"Nucleosome breathing and remodeling constrain CRISPR-Cas9 function","volume":"5","author":"Isaac","year":"2016","journal-title":"Elife"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.ymthe.2019.10.008","article-title":"Computational Analysis Concerning the Impact of DNA Accessibility on CRISPR-Cas9 Cleavage Efficiency","volume":"28","author":"Chung","year":"2020","journal-title":"Mol. Ther."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Kallimasioti-Pazi, E.M., Thelakkad Chathoth, K., Taylor, G.C., Meynert, A., Ballinger, T., Kelder, M.J.E., Lalevee, S., Sanli, I., Feil, R., and Wood, A.J. (2018). Heterochromatin delays CRISPR-Cas9 mutagenesis but does not influence the outcome of mutagenic DNA repair. PLoS Biol., 16, Correction in PLoS Biol. 2019, 17, e3000160.","DOI":"10.1371\/journal.pbio.3000160"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s13072-025-00573-x","article-title":"Impact of chromatin on HIV-1 latency: A multi-dimensional perspective","volume":"18","author":"Jones","year":"2025","journal-title":"Epigenet. Chromatin"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.gde.2016.05.013","article-title":"Nuclear compartmentalization of DNA repair","volume":"37","author":"Kalousi","year":"2016","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1073\/pnas.1013571108","article-title":"Methylation of histone H3 lysine 36 enhances DNA repair by nonhomologous end-joining","volume":"108","author":"Fnu","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1101\/gr.244293.118","article-title":"Accurate analysis of genuine CRISPR editing events with ampliCan","volume":"29","author":"Labun","year":"2019","journal-title":"Genome Res."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"28973","DOI":"10.1038\/srep28973","article-title":"CRISP-ID: Decoding CRISPR mediated indels by Sanger sequencing","volume":"6","author":"Dehairs","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/s41587-019-0032-3","article-title":"CRISPResso2 provides accurate and rapid genome editing sequence analysis","volume":"37","author":"Clement","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/nbt.3628","article-title":"CrispRVariants charts the mutation spectrum of genome engineering experiments","volume":"34","author":"Lindsay","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Hsiau, T., Conant, D., Rossi, N., Maures, T., Waite, K., Yang, J., Joshi, S., Kelso, R., Holden, K., and Enzmann, B.L. (2019). Inference of CRISPR Edits from Sanger Trace Data. bioRxiv.","DOI":"10.1101\/251082"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"4761","DOI":"10.1038\/s41467-023-40344-4","article-title":"Simultaneous inhibition of DNA-PK and Pol\u03f4 improves integration efficiency and precision of genome editing","volume":"14","author":"Wimberger","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"e168","DOI":"10.1093\/nar\/gku936","article-title":"Easy quantitative assessment of genome editing by sequence trace decomposition","volume":"42","author":"Brinkman","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.bj.2019.10.005","article-title":"CRISPR-Cas12a: Functional overview and applications","volume":"43","author":"Paul","year":"2020","journal-title":"Biomed. J."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1038\/nbt.3404","article-title":"Broadening the targeting range of Staphylococcus aureus CRISPR-Cas9 by modifying PAM recognition","volume":"33","author":"Kleinstiver","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1016\/j.gpb.2022.12.003","article-title":"Superior Fidelity and Distinct Editing Outcomes of SaCas9 Compared with SpCas9 in Genome Editing","volume":"21","author":"Yang","year":"2023","journal-title":"Genom. Proteom. Bioinform."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1080\/14712598.2021.1865302","article-title":"HIV-1 cure strategies: Why CRISPR?","volume":"21","author":"Atkins","year":"2021","journal-title":"Expert. Opin. Biol. Ther."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"e0135821","DOI":"10.1128\/JVI.01358-21","article-title":"CRISPR\/Cas9 Ablation of Integrated HIV-1 Accumulates Proviral DNA Circles with Reformed Long Terminal Repeats","volume":"95","author":"Lai","year":"2021","journal-title":"J. Virol."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Meyenberg, M., Ferreira da Silva, J., and Loizou, J.I. (2021). Tissue Specific DNA Repair Outcomes Shape the Landscape of Genome Editing. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.728520"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"554","DOI":"10.2174\/157016211798998736","article-title":"Control of HIV Latency by Epigenetic and Non-Epigenetic Mechanisms","volume":"9","author":"Mbonye","year":"2011","journal-title":"Curr. HIV Res."},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Jones, J.E., Gunderson, C.E., Wigdahl, B., and Nonnemacher, M.R. (2026). Breaking into HIV-1\u2019s Epigenetic Vault: Cure Strategies to Eliminate the Viral Reservoir. Viruses, 18.","DOI":"10.3390\/v18030354"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/bs.pmbts.2017.09.003","article-title":"Chapter Three\u2014Dynamics of Indel Profiles Induced by Various CRISPR\/Cas9 Delivery Methods","volume":"152","author":"Kosicki","year":"2017","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_155","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_156","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s13059-018-1445-x","article-title":"Systematic evaluation of CRISPR-Cas systems reveals design principles for genome editing in human cells","volume":"19","author":"Wang","year":"2018","journal-title":"Genome Biol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/nbt.3437","article-title":"Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9","volume":"34","author":"Doench","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"6413","DOI":"10.1038\/ncomms7413","article-title":"Use of the CRISPR\/Cas9 system as an intracellular defense against HIV-1 infection in human cells","volume":"6","author":"Liao","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s12977-015-0150-z","article-title":"The CRISPR\/Cas9 system inactivates latent HIV-1 proviral DNA","volume":"12","author":"Zhu","year":"2015","journal-title":"Retrovirology"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.virusres.2018.04.002","article-title":"Genome scale screening identification of SaCas9\/gRNAs for targeting HIV-1 provirus and suppression of HIV-1 infection","volume":"250","author":"Wang","year":"2018","journal-title":"Virus Res."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"5463","DOI":"10.1073\/pnas.74.12.5463","article-title":"DNA sequencing with chain-terminating inhibitors","volume":"74","author":"Sanger","year":"1977","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1186\/s43141-023-00587-6","article-title":"Mastering DNA chromatogram analysis in Sanger sequencing for reliable clinical analysis","volume":"21","author":"Hashim","year":"2023","journal-title":"J. Genet. Eng. Biotechnol."},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Sundquist, A., Ronaghi, M., Tang, H., Pevzner, P., and Batzoglou, S. (2007). Whole-genome sequencing and assembly with high-throughput, short-read technologies. PLoS ONE, 2.","DOI":"10.1371\/journal.pone.0000484"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1146\/annurev.genom.9.081307.164359","article-title":"Next-generation DNA sequencing methods","volume":"9","author":"Mardis","year":"2008","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.humimm.2021.02.012","article-title":"Next-generation sequencing technologies: An overview","volume":"82","author":"Hu","year":"2021","journal-title":"Hum. Immunol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"11461","DOI":"10.1073\/pnas.1405186111","article-title":"RNA-directed gene editing specifically eradicates latent and prevents new HIV-1 infection","volume":"111","author":"Hu","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"22555","DOI":"10.1038\/srep22555","article-title":"Elimination of HIV-1 Genomes from Human T-lymphoid Cells by CRISPR\/Cas9 Gene Editing","volume":"6","author":"Kaminski","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1038\/nbt.3583","article-title":"Analyzing CRISPR genome-editing experiments with CRISPResso","volume":"34","author":"Pinello","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Darcis, G., Binda, C.S., Klaver, B., Herrera-Carrillo, E., Berkhout, B., and Das, A.T. (2019). The Impact of HIV-1 Genetic Diversity on CRISPR-Cas9 Antiviral Activity and Viral Escape. Viruses, 11.","DOI":"10.3390\/v11030255"},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Atkins, A., Chung, C.H., Allen, A.G., Dampier, W., Gurrola, T.E., Sariyer, I.K., Nonnemacher, M.R., and Wigdahl, B. (2021). Off-Target Analysis in Gene Editing and Applications for Clinical Translation of CRISPR\/Cas9 in HIV-1 Therapy. Front. Genome Ed., 3.","DOI":"10.3389\/fgeed.2021.673022"},{"key":"ref_171","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_172","doi-asserted-by":"crossref","first-page":"W242","DOI":"10.1093\/nar\/gky354","article-title":"CRISPOR: Intuitive guide selection for CRISPR\/Cas9 genome editing experiments and screens","volume":"46","author":"Concordet","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1089\/crispr.2018.0020","article-title":"Prediction of Human Immunodeficiency Virus Type 1 Subtype-Specific Off-Target Effects Arising from CRISPR-Cas9 Gene Editing Therapy","volume":"1","author":"Link","year":"2018","journal-title":"Cris. J."},{"key":"ref_174","doi-asserted-by":"crossref","unstructured":"Dampier, W., Nonnemacher, M.R., Mell, J., Earl, J., Ehrlich, G.D., Pirrone, V., Aiamkitsumrit, B., Zhong, W., Kercher, K., and Passic, S. (2016). HIV-1 Genetic Variation Resulting in the Development of New Quasispecies Continues to Be Encountered in the Peripheral Blood of Well-Suppressed Patients. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0155382"},{"key":"ref_175","doi-asserted-by":"crossref","unstructured":"Xiao, Q., Guo, D., and Chen, S. (2019). Application of CRISPR\/Cas9-Based Gene Editing in HIV-1\/AIDS Therapy. Front. Cell. Infect. Microbiol., 9.","DOI":"10.3389\/fcimb.2019.00069"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/nm880","article-title":"Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells","volume":"9","author":"Siliciano","year":"2003","journal-title":"Nat. Med."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"17088","DOI":"10.1038\/s41598-019-52353-9","article-title":"Novel gRNA design pipeline to develop broad-spectrum CRISPR\/Cas9 gRNAs for safe targeting of the HIV-1 quasispecies in patients","volume":"9","author":"Sullivan","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1126\/science.1141453","article-title":"HIV-1 proviral DNA excision using an evolved recombinase","volume":"316","author":"Sarkar","year":"2007","journal-title":"Science"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"7771","DOI":"10.1093\/nar\/gkt571","article-title":"Zinc-finger-nucleases mediate specific and efficient excision of HIV-1 proviral DNA from infected and latently infected human T cells","volume":"41","author":"Qu","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1007\/s13365-014-0308-9","article-title":"Genome editing strategies: Potential tools for eradicating HIV-1\/AIDS","volume":"21","author":"Khalili","year":"2015","journal-title":"J. Neurovirol"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"6883","DOI":"10.1128\/JVI.78.13.6883-6890.2004","article-title":"The human immunodeficiency virus type 1 promoter contains a CATA box instead of a TATA box for optimal transcription and replication","volume":"78","author":"Kamoschinski","year":"2004","journal-title":"J. Virol."},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"Yuan, T., Li, J., and Zhang, M.Y. (2013). HIV-1 envelope glycoprotein variable loops are indispensable for envelope structural integrity and virus entry. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0069789"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"431","DOI":"10.2174\/1570162X14666160324125536","article-title":"HIV-1 Latency and Eradication: Past, Present and Future","volume":"14","author":"Datta","year":"2016","journal-title":"Curr. HIV Res."},{"key":"ref_184","doi-asserted-by":"crossref","unstructured":"Troyano-Hernaez, P., Reinosa, R., and Holguin, A. (2022). Genetic Diversity and Low Therapeutic Impact of Variant-Specific Markers in HIV-1 Pol Proteins. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.866705"},{"key":"ref_185","doi-asserted-by":"crossref","unstructured":"Chung, C.H., Allen, A.G., Atkins, A., Link, R.W., Nonnemacher, M.R., Dampier, W., and Wigdahl, B. (2021). Computational Design of gRNAs Targeting Genetic Variants Across HIV-1 Subtypes for CRISPR-Mediated Antiviral Therapy. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.593077"},{"key":"ref_186","doi-asserted-by":"crossref","unstructured":"Curlin, M.E., Zioni, R., Hawes, S.E., Liu, Y., Deng, W., Gottlieb, G.S., Zhu, T., and Mullins, J.I. (2010). HIV-1 envelope subregion length variation during disease progression. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1001228"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"15279","DOI":"10.1074\/jbc.M114.628610","article-title":"The V4 and V5 Variable Loops of HIV-1 Envelope Glycoprotein Are Tolerant to Insertion of Green Fluorescent Protein and Are Useful Targets for Labeling","volume":"290","author":"Nakane","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s12977-015-0148-6","article-title":"An integrated map of HIV genome-wide variation from a population perspective","volume":"12","author":"Li","year":"2015","journal-title":"Retrovirology"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/bs.aivir.2015.04.001","article-title":"Human Immunodeficiency Virus Type 1 Cellular Entry and Exit in the T Lymphocytic and Monocytic Compartments: Mechanisms and Target Opportunities During Viral Disease","volume":"93","author":"Aiamkitsumrit","year":"2015","journal-title":"Adv. Virus Res."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s12977-016-0266-9","article-title":"Utilization of HIV-1 envelope V3 to identify X4- and R5-specific Tat and LTR sequence signatures","volume":"13","author":"Antell","year":"2016","journal-title":"Retrovirology"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/B978-0-12-407698-3.00006-5","article-title":"Genetic variation and HIV-associated neurologic disease","volume":"87","author":"Dahiya","year":"2013","journal-title":"Adv. Virus Res."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.ebiom.2016.08.045","article-title":"Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity","volume":"12","author":"Bradley","year":"2016","journal-title":"EBioMedicine"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"27156","DOI":"10.1074\/jbc.M111.258855","article-title":"Highly conserved structural properties of the C-terminal tail of HIV-1 gp41 protein despite substantial sequence variation among diverse clades: Implications for functions in viral replication","volume":"286","author":"Steckbeck","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1097\/QAD.0b013e328011e691","article-title":"HIV-1 protease and reverse transcriptase mutations for drug resistance surveillance","volume":"21","author":"Shafer","year":"2007","journal-title":"AIDS"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"2696","DOI":"10.1128\/JVI.06591-11","article-title":"Characterization of the R263K mutation in HIV-1 integrase that confers low-level resistance to the second-generation integrase strand transfer inhibitor dolutegravir","volume":"86","author":"Quashie","year":"2012","journal-title":"J. Virol."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"1","DOI":"10.37796\/2211-8039.1422","article-title":"Mutation patterns of integrase gene affect antiretroviral resistance in various non-B subtypes of human immunodeficiency virus Type-1 and their implications for patients\u2019 therapy","volume":"13","author":"Djojosugito","year":"2023","journal-title":"BioMedicine"},{"key":"ref_197","doi-asserted-by":"crossref","unstructured":"Klingler, J., Anton, H., Real, E., Zeiger, M., Moog, C., Mely, Y., and Boutant, E. (2020). How HIV-1 Gag Manipulates Its Host Cell Proteins: A Focus on Interactors of the Nucleocapsid Domain. Viruses, 12.","DOI":"10.3390\/v12080888"},{"key":"ref_198","doi-asserted-by":"crossref","unstructured":"Troyano-Hernaez, P., Reinosa, R., and Holguin, A. (2022). HIV Capsid Protein Genetic Diversity Across HIV-1 Variants and Impact on New Capsid-Inhibitor Lenacapavir. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.854974"},{"key":"ref_199","doi-asserted-by":"crossref","unstructured":"Madlala, P., Mkhize, Z., Naicker, S., Khathi, S.P., Maikoo, S., Gopee, K., Dong, K.L., and Ndung\u2019u, T. (2023). Genetic variation of the HIV-1 subtype C transmitted\/founder viruses long terminal repeat elements and the impact on transcription activation potential and clinical disease outcomes. PLoS Pathog., 19.","DOI":"10.1101\/2023.02.09.527959"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"123605","DOI":"10.1155\/2012\/123605","article-title":"Impact of Tat Genetic Variation on HIV-1 Disease","volume":"2012","author":"Li","year":"2012","journal-title":"Adv. Virol."},{"key":"ref_201","first-page":"00006","article-title":"Role of Downstream Elements in Transcriptional Regulation of the HIV-1 Promoter","volume":"1","author":"Dahiya","year":"2014","journal-title":"J. Hum. Virol. Retrovirol."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"34532","DOI":"10.1038\/srep34532","article-title":"The variances of Sp1 and NF-kappaB elements correlate with the greater capacity of Chinese HIV-1 B\u2019-LTR for driving gene expression","volume":"6","author":"Qu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.jneuroim.2004.08.021","article-title":"Specific sequence configurations of HIV-1 LTR G\/C box array result in altered recruitment of Sp isoforms and correlate with disease progression","volume":"157","author":"Nonnemacher","year":"2004","journal-title":"J. Neuroimmunol."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1007\/s11481-010-9207-x","article-title":"Innate and adaptive factors regulating human immunodeficiency virus type 1 genomic activation","volume":"5","author":"Shah","year":"2010","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"2510","DOI":"10.1038\/srep02510","article-title":"Harnessing the CRISPR\/Cas9 system to disrupt latent HIV-1 provirus","volume":"3","author":"Ebina","year":"2013","journal-title":"Sci. Rep."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"41968","DOI":"10.1038\/srep41968","article-title":"A combinational CRISPR\/Cas9 gene-editing approach can halt HIV replication and prevent viral escape","volume":"7","author":"Lebbink","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1038\/mt.2016.24","article-title":"CRISPR-Cas9 Can Inhibit HIV-1 Replication but NHEJ Repair Facilitates Virus Escape","volume":"24","author":"Wang","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1038\/gt.2016.41","article-title":"Excision of HIV-1 DNA by gene editing: A proof-of-concept in vivo study","volume":"23","author":"Kaminski","year":"2016","journal-title":"Gene Ther."},{"key":"ref_209","first-page":"00022","article-title":"HIV Excision Utilizing CRISPR\/Cas9 Technology: Attacking the Proviral Quasispecies in Reservoirs to Achieve a Cure","volume":"1","author":"Dampier","year":"2014","journal-title":"MOJ Immunol."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"14413","DOI":"10.1038\/s41598-017-12612-z","article-title":"Designing broad-spectrum anti-HIV-1 gRNAs to target patient-derived variants","volume":"7","author":"Dampier","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_211","doi-asserted-by":"crossref","unstructured":"Allen, A.G., Chung, C.H., Worrell, S.D., Nwaozo, G., Madrid, R., Mele, A.R., Dampier, W., Nonnemacher, M.R., and Wigdahl, B. (2023). Assessment of anti-HIV-1 guide RNA efficacy in cells containing the viral target sequence, corresponding gRNA, and CRISPR\/Cas9. Front. Genome Ed., 5.","DOI":"10.3389\/fgeed.2023.1101483"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.celrep.2016.03.042","article-title":"CRISPR\/Cas9-Derived Mutations Both Inhibit HIV-1 Replication and Accelerate Viral Escape","volume":"15","author":"Wang","year":"2016","journal-title":"Cell Rep."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"2302","DOI":"10.1093\/nar\/gkm117","article-title":"Dynamic binding of Ku80, Ku70 and NF90 to the IL-2 promoter in vivo in activated T-cells","volume":"35","author":"Shi","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"119679","DOI":"10.1016\/j.bbamcr.2024.119679","article-title":"Simulated microgravity induces DNA damage concurrent with impairment of DNA repair and activation of cell-type specific DNA damage response in microglial and glioblastoma cells","volume":"1871","author":"Singh","year":"2024","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_215","doi-asserted-by":"crossref","unstructured":"Hussein, M., Molina, M.A., Berkhout, B., and Herrera-Carrillo, E. (2023). A CRISPR-Cas Cure for HIV\/AIDS. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021563"},{"key":"ref_216","doi-asserted-by":"crossref","unstructured":"Magro, G., Calistri, A., and Parolin, C. (2021). Targeting and Understanding HIV Latency: The CRISPR System against the Provirus. Pathogens, 10.","DOI":"10.3390\/pathogens10101257"},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1126\/science.1241475","article-title":"Structure of the CCR5 chemokine receptor-HIV entry inhibitor maraviroc complex","volume":"341","author":"Tan","year":"2013","journal-title":"Science"},{"key":"ref_218","doi-asserted-by":"crossref","unstructured":"Aiamkitsumrit, B., Dampier, W., Martin-Garcia, J., Nonnemacher, M.R., Pirrone, V., Ivanova, T., Zhong, W., Kilareski, E., Aldigun, H., and Frantz, B. (2014). Defining differential genetic signatures in CXCR4- and the CCR5-utilizing HIV-1 co-linear sequences. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0107389"},{"key":"ref_219","doi-asserted-by":"crossref","unstructured":"Naheed, F., Mumtaz, R., Shabbir, S., Jamil, A., Asif, A.R., Rahman, A., Ahmad, H.I., Essa, M., Akhtar, H., and Mahmoud, S.F. (2023). Structural and Phylogenetic Analysis of CXCR4 Protein Reveals New Insights into Its Role in Emerging and Re-Emerging Diseases in Mammals. Vaccines, 11.","DOI":"10.3390\/vaccines11030671"},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s13578-020-00410-6","article-title":"CCR5-Delta32 biology, gene editing, and warnings for the future of CRISPR-Cas9 as a human and humane gene editing tool","volume":"10","author":"Xu","year":"2020","journal-title":"Cell Biosci."},{"key":"ref_221","doi-asserted-by":"crossref","unstructured":"Mohamed, H., Gurrola, T., Berman, R., Collins, M., Sariyer, I.K., Nonnemacher, M.R., and Wigdahl, B. (2021). Targeting CCR5 as a Component of an HIV-1 Therapeutic Strategy. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.816515"},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1186\/1742-4690-10-130","article-title":"Modelling binding between CCR5 and CXCR4 receptors and their ligands suggests the surface electrostatic potential of the co-receptor to be a key player in the HIV-1 tropism","volume":"10","author":"Kalinina","year":"2013","journal-title":"Retrovirology"},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"9591","DOI":"10.1073\/pnas.1407473111","article-title":"Seamless modification of wild-type induced pluripotent stem cells to the natural CCR5Delta32 mutation confers resistance to HIV infection","volume":"111","author":"Ye","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"10852","DOI":"10.1038\/s41598-024-61626-x","article-title":"CRISPR\/Cas9 genome editing of CCR5 combined with C46 HIV-1 fusion inhibitor for cellular resistant to R5 and X4 tropic HIV-1","volume":"14","author":"Khamaikawin","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.omtm.2022.01.012","article-title":"CRISPR-Cas9-mediated gene disruption of HIV-1 co-receptors confers broad resistance to infection in human T cells and humanized mice","volume":"24","author":"Li","year":"2022","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/s41392-023-01514-4","article-title":"New case of HIV cure: Joined forces of haploidentical stem cells and HLA-mismatched cord blood","volume":"8","author":"Peterhoff","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/s41586-025-09893-0","article-title":"Sustained HIV-1 remission after heterozygous CCR5Delta32 stem cell transplantation","volume":"650","author":"Gaebler","year":"2026","journal-title":"Nature"},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1056\/NEJMoa0802905","article-title":"Long-term control of HIV by CCR5 Delta32\/Delta32 stem-cell transplantation","volume":"360","author":"Hutter","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1038\/s41586-019-1027-4","article-title":"HIV-1 remission following CCR5Delta32\/Delta32 haematopoietic stem-cell transplantation","volume":"568","author":"Gupta","year":"2019","journal-title":"Nature"},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1016\/j.cell.2023.02.030","article-title":"HIV-1 remission and possible cure in a woman after haplo-cord blood transplant","volume":"186","author":"Hsu","year":"2023","journal-title":"Cell"},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/d41586-024-02463-w","article-title":"Seventh patient \u2018cured\u2019 of HIV: Why scientists are excited","volume":"632","author":"Mallapaty","year":"2024","journal-title":"Nature"},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s13578-017-0174-2","article-title":"Genome editing of the HIV co-receptors CCR5 and CXCR4 by CRISPR-Cas9 protects CD4(+) T cells from HIV-1 infection","volume":"7","author":"Liu","year":"2017","journal-title":"Cell Biosci."},{"key":"ref_233","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."},{"key":"ref_234","doi-asserted-by":"crossref","unstructured":"Wang, W., Ye, C., Liu, J., Zhang, D., Kimata, J.T., and Zhou, P. (2014). CCR5 gene disruption via lentiviral vectors expressing Cas9 and single guided RNA renders cells resistant to HIV-1 infection. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0115987"},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/nbt.2507","article-title":"Targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease","volume":"31","author":"Cho","year":"2013","journal-title":"Nat. Biotechnol."},{"key":"ref_236","doi-asserted-by":"crossref","unstructured":"Kothandan, G., Gadhe, C.G., and Cho, S.J. (2012). Structural insights from binding poses of CCR2 and CCR5 with clinically important antagonists: A combined in silico study. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0032864"},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1099\/vir.0.000139","article-title":"Inhibition of HIV-1 infection of primary CD4+ T-cells by gene editing of CCR5 using adenovirus-delivered CRISPR\/Cas9","volume":"96","author":"Li","year":"2015","journal-title":"J. Gen. Virol."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/s41467-025-55873-3","article-title":"High frequency CCR5 editing in human hematopoietic stem progenitor cells protects xenograft mice from HIV infection","volume":"16","author":"Claiborne","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_239","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_240","doi-asserted-by":"crossref","unstructured":"Ruminski, P.G., Rettig, M.P., and DiPersio, J.F. (2024). Development of VLA4 and CXCR4 Antagonists for the Mobilization of Hematopoietic Stem and Progenitor Cells. Biomolecules, 14.","DOI":"10.3390\/biom14081003"},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"3813","DOI":"10.1038\/s41467-024-48228-x","article-title":"Replication competent HIV-guided CRISPR screen identifies antiviral factors including targets of the accessory protein Nef","volume":"15","author":"Laliberte","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1038\/nature15399","article-title":"HIV-1 Nef promotes infection by excluding SERINC5 from virion incorporation","volume":"526","author":"Rosa","year":"2015","journal-title":"Nature"},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"E7249-7256","DOI":"10.1073\/pnas.1516305112","article-title":"Specific induction of endogenous viral restriction factors using CRISPR\/Cas-derived transcriptional activators","volume":"112","author":"Bogerd","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"eabh3351","DOI":"10.1126\/scitranslmed.abh3351","article-title":"Genome-wide CRISPR screens identify combinations of candidate latency reversing agents for targeting the latent HIV-1 reservoir","volume":"14","author":"Dai","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/s41434-023-00413-1","article-title":"Targeted shock-and-kill HIV-1 gene therapy approach combining CRISPR activation, suicide gene tBid and retargeted adenovirus delivery","volume":"31","author":"Klinnert","year":"2024","journal-title":"Gene Ther."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s12981-022-00483-y","article-title":"CRISPR\/Cas9: A tool to eradicate HIV-1","volume":"19","author":"Bhowmik","year":"2022","journal-title":"AIDS Res. Ther."},{"key":"ref_247","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Arango, G., Li, F., Xiao, X., Putatunda, R., Yu, J., Yang, X.F., Wang, H., Watson, L.T., and Zhang, L. (2018). Comprehensive off-target analysis of dCas9-SAM-mediated HIV reactivation via long noncoding RNA and mRNA profiling. BMC Med. Genom., 11.","DOI":"10.1186\/s12920-018-0394-2"},{"key":"ref_248","doi-asserted-by":"crossref","unstructured":"Ortiz-Bueno, M., Zinghirino, F., Serra, P.P., Paschoudi, K., Montoliu, L., Atilla, E., Luo, Y., Cavazza, A., Lederer, C.W., and Benabdellah, K. (2026). From Bench to Bedside: Ethical and Clinical Best Practices for Genome Editing Applications. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27031484"},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.15252\/embr.201541337","article-title":"No time to waste--the ethical challenges created by CRISPR: CRISPR\/Cas, being an efficient, simple, and cheap technology to edit the genome of any organism, raises many ethical and regulatory issues beyond the use to manipulate human germ line cells","volume":"16","author":"Caplan","year":"2015","journal-title":"EMBO Rep."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"110","DOI":"10.3906\/biy-1912-52","article-title":"Bioethical issues in genome editing by CRISPR-Cas9 technology","volume":"44","author":"Ayanoglu","year":"2020","journal-title":"Turk. J. Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/5905\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T04:43:41Z","timestamp":1783053821000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/5905"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,30]]},"references-count":250,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27135905"],"URL":"https:\/\/doi.org\/10.3390\/ijms27135905","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,30]]}}}