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Development and characterization of a triple combination gene therapy vector inhibiting HIV‐1 multiplication
Author(s) -
Asparuhova Maria B.,
Barde Isabelle,
Trono Didier,
Schranz Karin,
Schümperli Daniel
Publication year - 2008
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.1238
Subject(s) - small hairpin rna , viral replication , biology , genetic enhancement , virology , viral vector , gene , vector (molecular biology) , rna , computational biology , genetics , virus , recombinant dna
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 © 2008 John Wiley & Sons, Ltd.