title: Development and characterization of a triple combination gene therapy vector inhibiting HIV-1 multiplication.
abstract: BACKGROUND
  RNA-based approaches are promising for long-term gene therapy against HIV-1. They can target virtually any step of the viral replication cycle. It is also possible to combine anti-HIV-1 transgenes targeting different facets of HIV replication to compensate for limitations of any individual construct, maximizing efficacy and decreasing chances of escape mutations. We have previously developed two strategies to inhibit HIV-1 multiplication. One was a short hairpin RNA targeting the host factor cyclophilin A implicated in HIV-1 replication. Additionally, an antisense derivative of U7 small nuclear RNA was designed to induce the skipping of the HIV-1 Tat and Rev internal exons.
  
  
  RESULTS
  In the present study, we have established an additional tRNAval promoter-driven shRNA against the coding sequence of viral infectivity factor. When human T-cell lines or primary CD4+ T cells are transduced with a triple lentiviral vector encoding these three therapeutic RNAs, HIV-1 multiplication is very efficiently suppressed. Moreover, all three therapeutic RNAs exhibit antiviral effects at early stages of the viral replication cycle (i.e. prior to viral cDNA integration or gene expression).
  
  
  CONCLUSIONS
  These findings make this triple lentiviral vector an attractive candidate for a gene therapy against HIV/AIDS.
authors.affiliation: Institute of Cell Biology, University of Bern, Bern, Switzerland.
authors.forename: Maria B
authors.initials: MB
authors.lastname: Asparuhova
authors.forename: Isabelle
authors.initials: I
authors.lastname: Barde
authors.forename: Didier
authors.initials: D
authors.lastname: Trono
authors.forename: Karin
authors.initials: K
authors.lastname: Schranz
authors.forename: Daniel
authors.initials: D
authors.lastname: Schümperli
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D015316:Genetic Therapy; D005822:Genetic Vectors; D015658:HIV Infections / Q000628:therapy; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D011401:Promoter Regions, Genetic; D016372:RNA, Antisense / Q000235:genetics / Q000378:metabolism*; D014161:Transduction, Genetic; D014779:Virus Replication / Q000235:genetics
chemical_list: D016372:RNA, Antisense