title: Combinatorial RNA-based gene therapy for the treatment of HIV/AIDS.
abstract: BACKGROUND
  HIV/AIDS continues to be a worldwide health problem and viral eradication has been an elusive goal. HIV+ patients are currently treated with combination antiretroviral therapy (cART) which is not curative. For many patients, cART is inaccessible, intolerable or unaffordable. Therefore, a new class of therapeutics for HIV is required to overcome these limitations. Cell and gene therapy for HIV has been proposed as a way to provide a functional cure for HIV in the form of a virus/infection resistant immune system.
  
  
  METHODS
  In this review, the authors describe the standard therapy for HIV/AIDS, its limitations, current areas of investigation and the potential of hematopoietic stem cells modified with anti-HIV RNAs as a means to affect a functional cure for HIV.
  
  
  CONCLUSIONS
  Cell and gene therapy for HIV/AIDS is a promising alternative to antiviral drug therapy and may provide a functional cure. In order to show clinical benefit, multiple mechanisms of inhibition of HIV entry and lifecycle are likely to be required. Among the most promising antiviral strategies is the use of transgenic RNA molecules that provide protection from HIV infection. When these molecules are delivered as gene-modified hematopoietic stem and progenitor cells, long-term repopulation of the patient's immune system with gene-modified progeny has been observed.
authors: Beckman Research Institute of City of Hope, Department of Molecular and Cell Biology, 1500 East Duarte Road, CA 91010, USA.
authors: Janet
authors: J
authors: Chung
authors: David L
authors: DL
authors: DiGiusto
authors: John J
authors: JJ
authors: Rossi
mesh_terms: D064987:Cell- and Tissue-Based Therapy; D003131:Combined Modality Therapy; D015316:Genetic Therapy; D015658:HIV Infections / Q000235:genetics / Q000628:therapy*; D015497:HIV-1 / Q000502:physiology*; D006412:Hematopoietic Stem Cells; D006801:Humans; D012313:RNA / Q000235:genetics*
chemical_list: D012313:RNA
references: Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11382-8
references: 8876144
references: Mol Ther. 2005 Jul;12(1):77-86
references: 15963923
references: MMWR Recomm Rep. 2002 May 17;51(RR-7):1-55
references: 12027060
references: Nat Med. 1996 Nov;2(11):1240-3
references: 8898752
references: Curr Opin Immunol. 2012 Oct;24(5):625-32
references: 22985479
references: Science. 1998 Jun 19;280(5371):1880-4
references: 9632380
references: Mol Ther. 2002 Apr;5(4):479-84
references: 11945076
references: Science. 1996 Apr 12;272(5259):263-7
references: 8602510
references: Nat Biotechnol. 2002 May;20(5):500-5
references: 11981565
references: Cell. 1996 Aug 9;86(3):367-77
references: 8756719
references: Antisense Nucleic Acid Drug Dev. 2000 Aug;10(4):251-61
references: 10984119
references: Blood. 2000 Dec 15;96(13):4103-10
references: 11110680
references: Nature. 1996 Jun 20;381(6584):661-6
references: 8649511
references: Blood. 2004 Feb 1;103(3):796-803
references: 12920024
references: Mol Ther. 2003 Aug;8(2):196-206
references: 12907142
references: Gene Ther. 2010 Mar;17(3):389-99
references: 19865182
references: Science. 1996 Jun 28;272(5270):1955-8
references: 8658171
references: AIDS. 2012 Jun 19;26(10):1293-302
references: 22706011
references: N Engl J Med. 2009 Feb 12;360(7):692-8
references: 19213682
references: Blood. 2011 Mar 10;117(10):2791-9
references: 21148083
references: J Exp Med. 1993 May 1;177(5):1331-42
references: 7683034
references: Blood. 2011 Mar 10;117(10):2746-7
references: 21393496
references: Science. 1996 Sep 27;273(5283):1856-62
references: 8791590
references: Blood. 1997 Apr 1;89(7):2259-67
references: 9116267
references: Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2804-8
references: 1372992
references: Sci Transl Med. 2010 Jun 16;2(36):36ra43
references: 20555022
references: N Engl J Med. 2009 Dec 3;361(23):2209-20
references: 19843557
references: Lancet. 1997 Sep 6;350(9079):741-2
references: 9291931
references: J Virol. 1999 Apr;73(4):2886-92
references: 10074136
references: Hum Mol Genet. 1996;5 Spec No:1397-404
references: 8875243
references: Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14047-52
references: 12376617
references: Gene Ther. 2002 Aug;9(16):1055-64
references: 12140733
references: Gene. 1994 Nov 4;149(1):33-9
references: 7958986
references: Mol Ther. 2005 Nov;12(5):900-9
references: 16115802
references: Nat Genet. 1997 Nov;17(3):314-7
references: 9354796
references: Blood. 2006 Mar 1;107(5):1751-60
references: 16269617