siRNAs, ribozymes and RNA decoys in modeling stem cell-based gene therapy for HIV/AIDS

Ramesh Akkina, Akhil Banerjea, Jirong Bai, Joseph S Anderson, Ming Jie Li, John Rossi

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

Gene therapy strategies for HIV infection require gene transduction of hematopoietic stem cells with effective therapeutic constructs. Here we summarize our studies on anti-HIV ribozymes, RNA decoys and the newly described siRNAs. The therapeutic constructs consisted of an anti-CCR5 ribozyme to down-regulate the HIV-1 cell surface co-receptor and ribozymes targeted to viral mRNAs coding for the tat, rev and env proteins. The RNA decoy targeted rev and the siRNA was directed against a sequence common to rev and tat mRNAs. CD34 hematopoietic progenitor cells were transduced with retroviral or lentiviral vectors containing these constructs. They were differentiated into macrophages in vitro and T cells in vivo in a SCID-hu mouse thymopoiesis model. The transgene-containing macrophages and T cells were found to be phenotypically normal. When challenged in vitro with HIV-1, they showed significant anti-viral resistance. These proof-of-concept studies demonstrated the utility of RNA-based anti-HIV constructs for gene therapy.

Original languageEnglish (US)
Pages (from-to)1997-2005
Number of pages9
JournalAnticancer Research
Volume23
Issue number3 A
StatePublished - May 2003
Externally publishedYes

    Fingerprint

Keywords

  • HIV gene therapy
  • Lentiviral vectors
  • Ribozymes
  • siRNAs
  • Stem cells

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Akkina, R., Banerjea, A., Bai, J., Anderson, J. S., Li, M. J., & Rossi, J. (2003). siRNAs, ribozymes and RNA decoys in modeling stem cell-based gene therapy for HIV/AIDS. Anticancer Research, 23(3 A), 1997-2005.