Silencing of HIV-1 gene expression by siRNAs in transduced cells.
The RNA interference (RNAi) phenomenon is a recently observed process in which the introduction of a double-stranded RNA (dsRNA) into cells causes the specific degradation of an mRNA containing the same sequence. To study dsRNA-mediated gene interference targeted to the env gene (NL4-3: 7490-7508) in HIV-1 infected cells, we constructed tandem-type and hairpin-type siRNA expression vectors, which were under the control of two U6 promoters. We also constructed lentiviral-based siRNA expression vectors for further assessment of their antiviral activity in transduced cells. At both the transient plasmid and lentiviral-mediated RNA expression levels, the siRNA encoding the env fragment exhibited sequence-specific suppression of target gene expression and strongly inhibited (> or = 90%) HIV-1 infection in the cells, as compared to the antisense RNA expression vector. Targeting the HIV-1 env gene with siRNAs encoding the env gene fragment (7490-7508) might be an effective strategy for gene therapy applications in HIV-1/AIDS treatment and management.
Hayafune
Masaaki
M
Department of Life and Environmental Science, Chiba Institute of Technology, Narashino-shi, Chiba, Japan.
Miyano-Kurosaki
Naoko
N
Takaku
Hiroshi
H
Park
Wee-Sung
WS
D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology*; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D020868:Gene Silencing / Q000187:drug effects; D015752:Genes, env / Q000187:drug effects / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008826:Microbial Sensitivity Tests; D034741:RNA, Small Interfering / Q000494:pharmacology*; D014161:Transduction, Genetic
D019380:Anti-HIV Agents; D034741:RNA, Small Interfering