Inhibition of HIV-1 infection by lentiviral vectors expressing Pol III-promoted anti-HIV RNAs

Ming Jie Li, Gerhard Bauer, Alessandro Michienzi, Jiing Kuan Yee, Nan Sook Lee, James Kim, Shirley Li, Daniela Castanotto, John Zaia, John J. Rossi

Research output: Contribution to journalArticlepeer-review

140 Scopus citations


A primary advantage of lentiviral vectors is their ability to pass through the nuclear envelope into the cell nucleus thereby allowing transduction of nondividing cells. Using HIV-based lentiviral vectors, we delivered an anti-CCR5 ribozyme (CCR5RZ), a nucleolar localizing TAR RNA decoy, or Pol III-expressed siRNA genes into cultured and primary cells. The CCR5RZ is driven by the adenoviral VA1 Pol III promoter, while the human U6 snRNA Pol III-transcribed TAR decoy is embedded in a U16 snoRNA (designated U16TAR), and the siRNAs were expressed from the human U6 Pol III promoter. The transduction efficiencies of these vectors ranged from 96-98% in 293 cells to 15-20% in primary PBMCs. A combination of the CCR5RZ and U16TAR decoy in a single vector backbone gave enhanced protection against HIV-1 challenge in a selective survival assay in both primary T cells and CD34+-derived monocytes. The lentiviral vector backbone-expressed siRNAs also showed potent inhibition of p24 expression in PBMCs challenged with HIV-1. Overall our results demonstrate that the lentiviral-based vectors can efficiently deliver single constructs as well as combinations of Pol III therapeutic expression units into primary hematopoietic cells for anti-HIV gene therapy and hold promise for stem or T-cell-based gene therapy for HIV-1 infection.

Original languageEnglish (US)
Pages (from-to)196-206
Number of pages11
JournalMolecular Therapy
Issue number2
StatePublished - Aug 1 2003
Externally publishedYes


  • CCR5
  • HIV-1 gene therapy
  • Lentiviral vector
  • Ribozyme
  • RNA decoy
  • siRNAs
  • TAR

ASJC Scopus subject areas

  • Molecular Biology


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