Long-term inhibition of HIV-1 infection in primary hematopoietic cells by lentiviral vector delivery of a triple combination of anti-HIV shRNA, anti-CCR5 ribozyme, and a nucleolar-localizing TAR decoy

Ming Jie Li, James Kim, Shirley Li, John Zaia, Jiing Kuan Yee, Joseph S Anderson, Ramesh Akkina, John J. Rossi

Research output: Contribution to journalArticle

197 Scopus citations


Combinatorial therapies for the treatment of HIV-1 infection have proven to be effective in reducing patient viral loads and slowing the progression to AIDS. We have developed a series of RNA-based inhibitors for use in a gene therapy-based treatment for HIV-1 infection. The transcriptional units have been inserted into the backbone of a replication-defective lentiviral vector capable of transducing a wide array of cell types, including CD34+ hematopoietic progenitor cells. The combinatorial therapeutic RNA vector harbors a U6 Pol III promoter-driven short hairpin RNA (shRNA) targeting the rev and tat mRNAs of HIV-1, a U6 transcribed nucleolar-localizing TAR RNA decoy, and a VA1-derived Pol III cassette that expresses an anti-CCR5 ribozyme. Each of these therapeutic RNAs targets a different gene product and blocks HIV infection by a distinct mechanism. Our results demonstrate that the combinatorial vector suppresses HIV replication long term in a more-than-additive fashion relative to the single shRNA or double shRNA/ ribozyme or decoy combinations. Our data demonstrate the validity and efficacy of a combinatorial RNA-based gene therapy for the treatment of HIV-1 infection.

Original languageEnglish (US)
Pages (from-to)900-909
Number of pages10
JournalMolecular Therapy
Issue number5
StatePublished - Nov 2005
Externally publishedYes



  • CCR5
  • HIV/AIDS gene therapy
  • Lentiviral vector
  • Ribozyme
  • RNA decoy
  • shRNA
  • TAR
  • Transgenic macrophages

ASJC Scopus subject areas

  • Molecular Biology

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