{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T17:45:21Z","timestamp":1793123121631,"version":"4.5.0"},"reference-count":23,"publisher":"National Academy of Sciences","issue":"46","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,11,14]]},"abstract":"<jats:p>We report findings from a clinical evaluation of lentiviral vectors in a phase I open-label nonrandomized clinical trial for HIV. This trial evaluated the safety of a conditionally replicating HIV-1-derived vector expressing an antisense gene against the HIV envelope. Five subjects with chronic HIV infection who had failed to respond to at least two antiviral regimens were enrolled. A single i.v. infusion of gene-modified autologous CD4 T cells was well tolerated in all patients. Viral loads were stable, and one subject exhibited a sustained decrease in viral load. CD4 counts remained steady or increased in four subjects, and sustained gene transfer was observed. Self-limiting mobilization of the vector was observed in four of five patients. There is no evidence for insertional mutagenesis after 21\u201336 months of observation. Immune function improved in four subjects. Lentiviral vectors appear promising for gene transfer to humans.<\/jats:p>","DOI":"10.1073\/pnas.0608138103","type":"journal-article","created":{"date-parts":[[2006,11,7]],"date-time":"2006-11-07T22:59:07Z","timestamp":1162940347000},"page":"17372-17377","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":411,"title":["Gene transfer in humans using a conditionally replicating lentiviral vector"],"prefix":"10.1073","volume":"103","author":[{"given":"Bruce L.","family":"Levine","sequence":"first","affiliation":[{"name":"*Abramson Family Cancer Research Institute, University of Pennsylvania Cancer Center,"},{"name":"Departments of \u2020Pathology and Laboratory Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent M.","family":"Humeau","sequence":"additional","affiliation":[{"name":"VIRxSYS Corporation, Gaithersburg, MD 20877; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Boyer","sequence":"additional","affiliation":[{"name":"Departments of \u2020Pathology and Laboratory Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob-Roy","family":"MacGregor","sequence":"additional","affiliation":[{"name":"Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tessio","family":"Rebello","sequence":"additional","affiliation":[{"name":"VIRxSYS Corporation, Gaithersburg, MD 20877; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobin","family":"Lu","sequence":"additional","affiliation":[{"name":"VIRxSYS Corporation, Gaithersburg, MD 20877; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwendolyn K.","family":"Binder","sequence":"additional","affiliation":[{"name":"VIRxSYS Corporation, Gaithersburg, MD 20877; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Slepushkin","sequence":"additional","affiliation":[{"name":"VIRxSYS Corporation, Gaithersburg, MD 20877; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck","family":"Lemiale","sequence":"additional","affiliation":[{"name":"VIRxSYS Corporation, Gaithersburg, MD 20877; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Mascola","sequence":"additional","affiliation":[{"name":"**Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic D.","family":"Bushman","sequence":"additional","affiliation":[{"name":"Microbiology, University of Pennsylvania, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boro","family":"Dropulic","sequence":"additional","affiliation":[{"name":"VIRxSYS Corporation, Gaithersburg, MD 20877; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl H.","family":"June","sequence":"additional","affiliation":[{"name":"*Abramson Family Cancer Research Institute, University of Pennsylvania Cancer Center,"},{"name":"Departments of \u2020Pathology and Laboratory Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2006,11,14]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5270.1939"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.13.7079-7088.2004"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/jgm.593"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0102-47"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2004.03.005"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2005.16.17"},{"key":"e_1_3_4_7_2","first-page":"39","volume":"2","author":"Schonely K","year":"2003","unstructured":"K Schonely, C Afable, V Slepushkin, X Lu, K Andre, J Boehmer, K Bengston, M Doub, R Cohen, D Berlinger, et al. Bioprocessing J 2, 39\u201347 (2003).","journal-title":"Bioprocessing J"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5259.263"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1006\/mthe.2002.0611"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.9.5316"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0400606101"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.20.11103"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.18.10028-10036.2003"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1088547"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0020234"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00864-4"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1083413"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.11.6610-6619.2005"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/173.2.340"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2005.01.010"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1086\/380098"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2005.16.1241"},{"key":"e_1_3_4_23_2","first-page":"2028","volume":"12","author":"MacGregor RR","year":"2001","unstructured":"RR MacGregor Hum Gene Ther 12, 2028\u20132029 (2001).","journal-title":"Hum Gene Ther"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0608138103","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T15:46:13Z","timestamp":1649778373000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0608138103"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,11,14]]},"references-count":23,"journal-issue":{"issue":"46","published-print":{"date-parts":[[2006,11,14]]}},"alternative-id":["10.1073\/pnas.0608138103"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0608138103","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,11,14]]},"assertion":[{"value":"2006-06-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2006-11-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}