Inhibition of HIV-1 by lentiviral vector-transduced siRNAs in T lymphocytes differentiated in SCID-hu mice and CD34+ progenitor cell-derived macrophages

Akhil Banerjea, Ming Jie Li, Gerhard Bauer, Leila Remling, Nan Sook Lee, John Rossi, Ramesh Akkina

Research output: Contribution to journalArticle

155 Scopus citations

Abstract

The phenomenon of RNA interference mediated by small interfering RNAs (siRNAs) is a potent gene-silencing mechanism. A number of recent studies demonstrated inhibition of HIV-1 replication in cultured cells using this approach. To make further progress and harness this technology for HIV-1 gene therapy in a stem cell setting, in vivo studies using primary hematopoietic cells are needed. Using an HIV-based lentiviral vector we introduced an anti-Rev siRNA construct into CD34+ hematopoietic progenitor cells. The siRNA-transduced progenitor cells were allowed to mature into macrophages in vitro and T cells in vivo in SCID-hu mouse thy/liv grafts. Phenotypically normal T cells and macrophages displaying characteristic surface markers were obtained. In vitro HIV-1 challenge of the siRNA-expressing macrophages and T cells with macrophage-tropic and T-cell-tropic HIV-1, respectively, showed marked viral resistance. These experiments demonstrate the utility of siRNAs delivered into hematopoietic stem cells via lentiviral vectors for future in vivo applications.

Original languageEnglish (US)
Pages (from-to)62-71
Number of pages10
JournalMolecular Therapy
Volume8
Issue number1
DOIs
StatePublished - Jul 1 2003
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Biology

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