title: RNAi-inducing lentiviral vectors for anti-HIV-1 gene therapy.
abstract: RNA interference (RNAi)-based gene therapy for the treatment of HIV-1 infection provides a novel antiviral approach. For delivery of RNAi inducers to CD4+ T cells or CD34+ blood stem cells, lentiviral vectors are attractive because of their ability to transduce nondividing cells. In addition, lentiviral vectors allow stable transgene expression by inserting their cargo into the host cell genome. However, use of the HIV-1-based lentiviral vector also creates specific problems. The RNAi inducers can target HIV-1 sequences in the genomic RNA of the lentiviral vector. As the RNAi-inducing cassette contains palindromic sequences, the lentiviral vector RNA genome will have a perfect target sequence for the expressed RNAi inducer. Vectors encoding microRNAs face the putative problem that the vector RNA genome can be inactivated by Drosha processing. Here, we describe the design of lentiviral vectors with single or multiple RNAi-inducing antiviral cassettes. The possibility of titer reduction and some effective countermeasures are also presented.
authors: Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. y.p.liu@amc.uva.nl
authors: Ying Poi
authors: YP
authors: Liu
authors: Jan-Tinus
authors: JT
authors: Westerink
authors: Olivier
authors: O
authors: ter Brake
authors: Ben
authors: B
authors: Berkhout
mesh_terms: D001483:Base Sequence; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics*; D015658:HIV Infections / Q000235:genetics* / Q000628:therapy*; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D008969:Molecular Sequence Data; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D035683:MicroRNAs; D034741:RNA, Small Interfering