Lentiviral vectors for gene therapy of HIV-1 infection.
Lentiviral vectors based on HIV-1, HIV-2, or SIV have the ability to transduce dividing and non-dividing T cells, dendritic cells, hematopoietic stem cells and macrophages, which are the main target cells for gene therapy of HIV-1 infection. Besides their function as gene delivery vehicles, lentiviral vector backbones containing the cis-acting sequences necessary to perform a complete replication cycle in the presence of viral proteins provided in trans, have the ability to inhibit HIV-1 replication by several mechanisms that include sequestration of the regulatory proteins Tat and Rev, competition for packaging into virions and possibly by inhibition of reverse transcription in heterodimeric virions. Expression of anti-HIV-1 genes in these vectors would strengthen the potency of this inhibition. To avoid self-inhibition of the vector packaging system, lentiviral vectors have to be modified to become resistant to the anti-HIV-1 genes encoded by them. This review discusses the different genetic intervention strategies for gene therapy of HIV-1 infection focusing in the use of lentiviral vectors as the main agents to mediate inhibition of HIV-1 replication. It also discusses possible strategies to adapt HIV-1 or HIV-2 vectors to express the different classes of anti-HIV-1 genes and approaches to improve in vivo vector mobilization.
Clinical Gene Therapy Branch, National Human Genome Research Institute, National Institutes of Health, 10 Center Drive, Bldg. 10, Room 10C103, Bethesda, MD 20892, USA. mmautino@nhgri.nih.gov
Mario R
MR
Mautino
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D004268:DNA-Binding Proteins; D015694:Gene Products, rev / Q000235:genetics; D015696:Gene Products, tat / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics*; D015658:HIV Infections / Q000628:therapy*; D015497:HIV-1 / Q000235:genetics; D015498:HIV-2 / Q000235:genetics; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D016372:RNA, Antisense / Q000378:metabolism; D016337:RNA, Catalytic / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D015302:Simian Immunodeficiency Virus / Q000235:genetics; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D015694:Gene Products, rev; D015696:Gene Products, tat; C489559:KHDRBS1 protein, human; D016372:RNA, Antisense; D016337:RNA, Catalytic; D016601:RNA-Binding Proteins; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus