INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 BY RETROVIRAL VECTORS EXPRESSING ANTISENSE-TAR

被引:32
作者
CHUAH, MKL
VANDENDRIESSCHE, T
CHANG, HK
ENSOLI, B
MORGAN, RA
机构
[1] NIH,NATL CTR HUMAN GENOME RES,CLIN GENE THERAPY BRANCH,BETHESDA,MD 20892
[2] GENET THERAPY INC,GAITHERSBURG,MD 20878
[3] NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892
关键词
D O I
10.1089/hum.1994.5.12-1467
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
The human immunodeficiency virus type-1 (HIV-1) Tat activation response (TAR) region is essential for Tat-mediated trans-activation of the HIV-I long terminal repeat (LTR), The TAR element is present on the 5' and 3' ends of all HIV-1 transcripts and is relatively conserved among different HIV-1 isolates. These properties make it an attractive target for anti-HIV-1 gene therapy strategies, We have constructed a Moloney murine leukemia-based retroviral vector that expresses a chimeric tRNA(i)Met-antisense TAR fusion transcript complementary to the HIV-1 TAR region. The potential of this anti-TAR retroviral vector to inhibit HIV-1 was initially tested by transient transfections with an HIV-1-LTR-Tat expression plasmid into HeLa-CAT cells, Anti-TAR inhibited Tat-mediated HIV-1 LTR-driven CAT reporter gene expression in a dose-dependent fashion, The antisense-TAR vector was then used to transduce the human SupT1 T cell line, Cotransfection of these SupT1 cells with a Tat expression plasmid plus an HIV-1 LTR-CAT reporter plasmid resulted in decreased CAT gene expression in comparison to control transduced SupT1 cells, The antisense-TAR engineered SupT1 cell line was then challenged with HIV-1(MN). HIV-1 viral production was inhibited in SupT1 cells transduced with the antisense-TAR retroviral vector, Greater inhibition of HIV-1 was observed with antisense-TAR as compared to antisense-Tat expressing retroviral vector, These observations suggest that antisense-TAR retroviral vectors are potentially useful for clinical anti-HIV-1 gene therapy.
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收藏
页码:1467 / 1475
页数:9
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