siRNAs, ribozymes and RNA decoys in modeling stem cell-based gene therapy for HIV/AIDS.
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.
Akkina
Ramesh
R
Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523-1619, USA. akkina@colostate.edu
Banerjea
Akhil
A
Bai
Jirong
J
Anderson
Joseph
J
Li
Ming-Jie
MJ
Rossi
John
J
D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000628:therapy*; D000818:Animals; D001483:Base Sequence; D015316:Genetic Therapy / Q000379:methods*; D015658:HIV Infections / Q000235:genetics / Q000628:therapy*; D015497:HIV-1 / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D009690:Nucleic Acid Conformation; D016337:RNA, Catalytic / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics*; D012367:RNA, Viral / Q000235:genetics*; D014161:Transduction, Genetic
D016337:RNA, Catalytic; D034741:RNA, Small Interfering; D012367:RNA, Viral