Document Detail


Specific HIV-1 env gene silencing by small interfering RNAs in human peripheral blood mononuclear cells.
MedLine Citation:
PMID:  14566364     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
W-S Park; M Hayafune; N Miyano-Kurosaki; H Takaku
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Gene therapy     Volume:  10     ISSN:  0969-7128     ISO Abbreviation:  Gene Ther.     Publication Date:  2003 Nov 
Date Detail:
Created Date:  2003-10-20     Completed Date:  2003-12-15     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9421525     Medline TA:  Gene Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  2046-50     Citation Subset:  IM    
Affiliation:
Department of Industrial Chemistry, Faculty of Engineering, Chiba Institute of Technology, Tsudanuma, Narashino, Chiba, Japan.
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MeSH Terms
Descriptor/Qualifier:
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:
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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