Negative feedback inhibition of HIV-1 by TAT-inducible expression of siRNA

Hoshang J. Unwalla, Ming Jie Li, James D. Kim, Hai Tang Li, Ali Ehsani, Jessica Alluin, John J. Rossi

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1573-1578
Number of pages6
JournalNature Biotechnology
Volume22
Issue number12
DOIs
StatePublished - Dec 1 2004
Externally publishedYes

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