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Science 27 November 1992:
Vol. 258. no. 5087, pp. 1485 - 1488
DOI: 10.1126/science.1359646
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Articles

Science, Vol 258, Issue 5087, 1485-1488
Copyright © 1992 by American Association for the Advancement of Science

articles

Dual-target inhibition of HIV-1 in vitro by means of an adeno-associated virus antisense vector

S Chatterjee, PR Johnson, and KK Wong Jr

Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Rockville, MD 20852.

An adeno-associated virus vector encoding an antisense RNA was used to transduce stable intracellular resistance to human immunodeficiency virus-1 (HIV-1) in human hemopoietic and non-hemopoietic cell lines. The antisense targets are present in all HIV-1 transcripts and include the TAR sequence, which is critical for transcription and virus replication, and the polyadenylation signal. Cell lines expressing antisense RNA showed up to 95 percent inhibition of gene expression directed by the HIV-1 long terminal repeat and greater than 99 percent reduction in infectious HIV-1 production, with no detectable cellular toxicity. Because of their efficient transcription and inability to recombine with HIV-1, adeno-associated virus vectors represent a promising form of anti-retroviral gene therapy.


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