Gene-targeted inhibition of transactivation of human immunodeficiency virus type-1 (HIV-1)-LTR by antisense oligonucleotides |
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| Authors: | I. Demirhan O. Hasselmayer D. Hofmann A. Chandra F. P. Svinarchuk V. V. Vlassov J. Engels Professor P. Chandra |
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| Affiliation: | (1) Laboratory of Molecular Biology, Frankfurt University School of Medicine, 60590 Frankfurt, FRG;(2) Institute of Bioorganic Chemistry, Siberian Division of the Russian Academy of Sciences, Novosibirsk;(3) Institute of Organic Chemistry, Frankfurt University, FRG |
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| Abstract: | We have used an in vitro approach to study the efficiency of antisense oligonucleotides in inhibiting LTR-(HIV-1)-directed CAT expression catalyzed by tat protein, the functional protein of the transactivator gene. We selected the target sequence localized near the 5 end of the tat mRNA. The following conclusions can be drawn from the data presented here: a) Antisense oligonucleotides modified by conjugation of cholesterol at the 3 end have a severalfold higher inhibitory response, b) inhibitory response is dependent on the mode of introducing oligonucleotides, and c) the inhibition by antisense oligonucleotides is sequence specific and directed towards the targeted region. This approach could be useful for targeting functional regions of regulatory gene products and designing gene-targeted inhibitors of virus replication.Dedicated to Professor Klaus Ring on his 60th birthday. |
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| Keywords: | transactivation tat expression antisense oligonucleotides anti-tat-IgG |
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