{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:34:21Z","timestamp":1792787661828,"version":"4.5.0"},"reference-count":49,"publisher":"SAGE Publications","issue":"21-22","license":[{"start":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:00:00Z","timestamp":1787443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:00:00Z","timestamp":1787443200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"National Institute of Mental Health\/NIH","award":["P30MH092177"],"award-info":[{"award-number":["P30MH092177"]}]},{"name":"National Institute on Aging","award":["R01AG060962"],"award-info":[{"award-number":["R01AG060962"]}],"id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2026,11,1]]},"abstract":"<jats:p>\n                    Total elimination of replication-competent human immunodeficiency virus type 1 (HIV-1) remains a major clinical challenge, in part due to random integration of the proviral DNA into host cell chromosomes, which enables lifelong persistence and production of progeny. Although antiretroviral therapies (ARTs) suppress viral replication, they cannot eliminate integrated proviral DNA, which remains a fundamental obstacle to achieving a cure. To overcome this problem, we developed a combinatorial clustered regularly interspaced short palindromic repeats\u2013Cas9 gene editing strategy to disrupt viral replication and inactivate host factors essential for HIV-1 entry and spread. This approach targets C-C chemokine receptor type 5 (CCR5), a chemokine receptor central to HIV-1 host cell entry, and mannosyl-oligosaccharide glucosidase (MOGS), a key enzyme in glycoprotein processing that modifies the HIV-1 envelope glycoprotein gp120, facilitating receptor engagement, viral entry, and morphogenesis of infectious virion. We demonstrate that our strategy, which includes editing of the integrated proviral DNA, in concert with two cellular genes whose products facilitate viral entry, results in robust suppression of viral replication\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    and in\n                    <jats:italic toggle=\"yes\">ex vivo<\/jats:italic>\n                    -infected cells. Using transmission electron microscopy, HIV-1 p24 ELISA, and GFP-based viral infection assays, we show that the combination knockout of CCR5, MOGS, and viral sequences profoundly reduces HIV-1 replication in an\n                    <jats:italic toggle=\"yes\">ex vivo<\/jats:italic>\n                    cellular model, that is, HIV-1-infected peripheral blood mononuclear human cells, thus offering a pathway to launch further preclinical studies.\n                  <\/jats:p>","DOI":"10.1177\/10430342261463565","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T06:39:35Z","timestamp":1787553575000},"page":"1027-1044","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Triple-Target CRISPR Strategy to Block HIV Entry and Replication in Permissive Cells"],"prefix":"10.1177","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9507-8174","authenticated-orcid":false,"given":"Zahra","family":"Safaei","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology, and Inflammation, Center for Neurovirology and Gene Editing, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Bellizzi","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Inflammation, Center for Neurovirology and Gene Editing, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Inflammation, Center for Neurovirology and Gene Editing, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuru","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Inflammation, Center for Neurovirology and Gene Editing, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilker K.","family":"Sariyer","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Inflammation, Center for Neurovirology and Gene Editing, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6819-5217","authenticated-orcid":false,"given":"Kamel","family":"Khalili","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Inflammation, Center for Neurovirology and Gene Editing, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,8,23]]},"reference":[{"key":"e_1_3_5_2_1","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2003.91"},{"key":"e_1_3_5_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep02510"},{"key":"e_1_3_5_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12977-015-0150-z"},{"key":"e_1_3_5_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000001079"},{"key":"e_1_3_5_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7413"},{"key":"e_1_3_5_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1405186111"},{"key":"e_1_3_5_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-017-2479-z"},{"key":"e_1_3_5_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep41968"},{"key":"e_1_3_5_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/v12030330"},{"key":"e_1_3_5_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/v12111223"},{"key":"e_1_3_5_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep31527"},{"key":"e_1_3_5_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2016.41"},{"key":"e_1_3_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2017.03.012"},{"key":"e_1_3_5_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19821-7"},{"key":"e_1_3_5_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10366-y"},{"key":"e_1_3_5_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep22555"},{"key":"e_1_3_5_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005953"},{"issue":"4","key":"e_1_3_5_19_1","first-page":"220","article-title":"Toward the cure of HIV-1 infection: Lessons learned and yet to be learned as new strategies are developed","volume":"20","author":"Jacobson JM","year":"2018","unstructured":"18.Jacobson JM, , and Khalili K. 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