Journal
NATURE BIOTECHNOLOGY
Volume 22, Issue 12, Pages 1573-1578Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nbt1040
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Funding
- NHLBI NIH HHS [HL074704] Funding Source: Medline
- NIAID NIH HHS [AI 29329, AI42552] Funding Source: Medline
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Here we demonstrate that an inducible anti-HIV short hairpin RNA (shRNA) expressed from a Pol II promoter inhibits HIV-1 gene expression in mammalian cells. Our strategy is based on a promoter system in which the HIV-1 LTR is fused to the Drosophila hsp70 minimal heat shock promoter. This system is inducible by HIV-1 TAT, which functions in a negative feedback loop to activate transcription of an shRNA directed against HIV-1 rev. Upon induction the shRNA is processed to an siRNA that guides inhibition of HIV replication in cultured T-lymphocytes and hematopoietic stem cell-derived monocytes. The fusion promoter system may be safer than drug-inducible systems for shRNA-mediated gene therapy against HIV as the shRNAs are only expressed following HIV infection.
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