期刊
JOURNAL OF GENE MEDICINE
卷 10, 期 10, 页码 1059-1070出版社
JOHN WILEY & SONS LTD
DOI: 10.1002/jgm.1238
关键词
cyclophilin A; exon skipping; HIV; RNA interference; U7 snRNA; viral infectivity factor
资金
- Swiss AIDS Research Program [3339-63429]
- European Network of Excellence on alternative splicing (EURASNET)
- Swiss National Science Foundation
Background RNA-based approaches are promising for long-term gene therapy against HIV-1. They can target Virtually any step of the vital replication cycle. It is also possible to combine anti-HIV-1 transgenes targeting different facets of HIV replication to compensate for limitations of ally 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.
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