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Specific HIV-1 env gene silencing by small interfering RNAs in human peripheral blood mononuclear cells.
- Source :
-
Gene therapy [Gene Ther] 2003 Nov; Vol. 10 (24), pp. 2046-50. - Publication Year :
- 2003
-
Abstract
- RNA interference (RNAi) is triggered by the presence of a double-stranded RNA (dsRNA) in the cell, and results in the silencing of homologous gene expression by the specific degradation of an mRNA containing the same sequence. dsRNA-mediated RNAi can be used in a wide variety of eucaryotes to induce the sequence-specific inhibition of gene expression. Synthetic 21-23 nucleotide (nt) small interfering RNAs (siRNAs) with 2-nt 3' overhangs were recently found to mediate efficient sequence-specific mRNA degradation in mammalian cells. Here, we show that synthetic siRNAs targeted against the viral structural Env proteins encoded by HIV-1 can specifically suppress the expression of HIV-1 genes. The siRNA-mediated RNAi also had advantages over antisense RNA-mediated inhibition, in terms of both the ease of designing effective antiviral agents and their potency. Especially, our best env-specific siRNAs, E7145 targeted to the central region of the V3 loop and E7490 targeted to the CD4 binding site of conserved regions on gp120, significantly inhibited the HIV-1 gene expression. Furthermore, E7145 and E7490 were effective against HIV-1(NL4-3) replication in PBMCs for a relatively long time (14 days). Therefore, the use of synthetic siRNAs provides a simple, rapid, and cost-effective tool for new anti-HIV-1 gene therapeutics.
- Subjects :
- Animals
Base Sequence
COS Cells
Cells, Cultured
Genetic Therapy methods
HIV-1 physiology
Humans
Molecular Sequence Data
RNA Interference
RNA, Messenger genetics
RNA, Viral genetics
Virus Replication
Gene Silencing
Genes, env genetics
HIV-1 genetics
Leukocytes, Mononuclear virology
RNA, Small Interfering genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0969-7128
- Volume :
- 10
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Gene therapy
- Publication Type :
- Academic Journal
- Accession number :
- 14566364
- Full Text :
- https://doi.org/10.1038/sj.gt.3302099