Enhanced gene silencing of HIV-1 specific siRNA using microRNA designed hairpins

Daniel Boden, Oliver Pusch, Rebecca Silbermann, Fred Lee, Lynne Tucker, Bharat Ramratnam

Research output: Contribution to journalArticlepeer-review

202 Scopus citations

Abstract

Post-transcriptional inhibition of HIV-1 replication can be achieved by RNA interference (RNAi). The cellular expression of short interfering RNA (siRNA) or short hairpin RNA (shRNA) homologous to regions of the HIV-1 genome decreases viral replication by the selective degradation of targeted RNA. Here, we demonstrate that another class of noncoding regulatory RNA, termed microRNA (miRNA), can be used to deliver antiviral RNAi. By incorporating sequences encoding siRNA targeting the HIV-1 transactivator protein tat into a human miR-30 pre-microRNA (pre-miRNA) backbone, we were able to express tat siRNA in cells. The tat siRNA delivered as pre-miRNA precursor was 80% more effective in reducing HIV-1 p24 antigen production than tat siRNA expressed as conventional shRNA. Our results confirm the utility of expressing HIV-1 specific siRNA through a miR-30 precursor stem-loop structure and suggest that this strategy can be used to increase the antiviral potency of RNAi.

Original languageEnglish (US)
Pages (from-to)1154-1158
Number of pages5
JournalNucleic acids research
Volume32
Issue number3
DOIs
StatePublished - 2004
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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