| Specific HIV-1 env gene silencing by small interfering RNAs in human peripheral blood mononuclear cells. | |
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MedLine Citation:
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PMID: 14566364 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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W-S Park; M Hayafune; N Miyano-Kurosaki; H Takaku |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Gene therapy Volume: 10 ISSN: 0969-7128 ISO Abbreviation: Gene Ther. Publication Date: 2003 Nov |
Date Detail:
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Created Date: 2003-10-20 Completed Date: 2003-12-15 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9421525 Medline TA: Gene Ther Country: England |
Other Details:
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Languages: eng Pagination: 2046-50 Citation Subset: IM |
Affiliation:
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Department of Industrial Chemistry, Faculty of Engineering, Chiba Institute of Technology, Tsudanuma, Narashino, Chiba, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Base Sequence COS Cells Cells, Cultured Gene Silencing* Gene Therapy / methods Genes, env / genetics* HIV-1 / genetics*, physiology Humans Leukocytes, Mononuclear / virology* Molecular Sequence Data RNA Interference RNA, Messenger / genetics RNA, Small Interfering / genetics* RNA, Viral / genetics Virus Replication |
| Chemical | |
Reg. No./Substance:
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0/RNA, Messenger; 0/RNA, Small Interfering; 0/RNA, Viral |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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