Document 0797 DOCN M9590797 TI Inhibition of clinical human immunodeficiency virus (HIV) type 1 isolates in primary CD4+ T lymphocytes by retroviral vectors expressing anti-HIV genes. DT 9509 AU Vandendriessche T; Chuah MK; Chiang L; Chang HK; Ensoli B; Morgan RA; Clinical Gene Therapy Branch, National Cancer Institute,; Bethesda, Maryland 20892, USA. SO J Virol. 1995 Jul;69(7):4045-52. Unique Identifier : AIDSLINE MED/95287453 AB Gene therapy may be of benefit in human immunodeficiency virus type 1 (HIV-1)-infected individuals by virtue of its ability to inhibit virus replication and prevent viral gene expression. It is not known whether anti-HIV-1 gene therapy strategies based on antisense or transdominant HIV-1 mutant proteins can inhibit the replication and expression of clinical HIV-1 isolates in primary CD4+ T lymphocytes. We therefore transduced CD4+ T lymphocytes from uninfected individuals with retroviral vectors expressing either HIV-1-specific antisense-TAR or antisense-Tat/Rev RNA, transdominant HIV-1 Rev protein, and a combination of antisense-TAR and transdominant Rev. The engineered CD4+ T lymphocytes were then infected with four different clinical HIV-1 isolates. We found that replication of all HIV-1 isolates was inhibited by all the anti-HIV vectors tested. Greater inhibition of HIV-1 was observed with transdominant Rev than with antisense RNA. We hereby demonstrated effective protection by antisense RNA or transdominant mutant proteins against HIV-1 infection in primary CD4+ T lymphocytes using clinical HIV-1 isolates, and this represents an essential step toward clinical anti-HIV-1 gene therapy. DE Acquired Immunodeficiency Syndrome/*THERAPY CD4-Positive T-Lymphocytes/*VIROLOGY *Gene Therapy Genetic Vectors Human HIV-1/*GENETICS Retroviridae/GENETICS RNA, Antisense/*THERAPEUTIC USE Support, Non-U.S. Gov't Zidovudine/PHARMACOLOGY JOURNAL ARTICLE SOURCE: National Library of Medicine. NOTICE: This material may be protected by Copyright Law (Title 17, U.S.Code).