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. Copyright (c) 2008 John Wiley & Sons, Ltd.
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. Copyright (c) 2008 John Wiley & Sons, Ltd.
Authors: David L DiGiusto; Amrita Krishnan; Lijing Li; Haitang Li; Shirley Li; Anitha Rao; Shu Mi; Priscilla Yam; Sherri Stinson; Michael Kalos; Joseph Alvarnas; Simon F Lacey; Jiing-Kuan Yee; Mingjie Li; Larry Couture; David Hsu; Stephen J Forman; John J Rossi; John A Zaia Journal: Sci Transl Med Date: 2010-06-16 Impact factor: 17.956
Authors: Susanne Przybylski; Michaela Gasch; Anne Marschner; Marcus Ebert; Alexander Ewe; Gisa Helmig; Nadja Hilger; Stephan Fricke; Susanne Rudzok; Achim Aigner; Jana Burkhardt Journal: PLoS One Date: 2017-05-02 Impact factor: 3.240