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Disease-Causing Allele-Specific Silencing by RNA Interference

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Author(s): Hirohiko Hohjoh

Journal: Pharmaceuticals
ISSN 1424-8247

Volume: 6;
Issue: 4;
Start page: 522;
Date: 2013;
Original page

Keywords: RNAi | allele-specific silencing | siRNA selection | dominantly inherited disease | nucleotide variation | allele discrimination | siRNA modification | forked siRNA

ABSTRACT
Small double-stranded RNAs (dsRNAs) of approximately 21-nucleotides in size, referred to as small interfering RNA (siRNA) duplexes, can induce sequence-specific posttranscriptional gene silencing, or RNA interference (RNAi). Since chemically synthesized siRNA duplexes were found to induce RNAi in mammalian cells, RNAi has become a powerful reverse genetic tool for suppressing the expression of a gene of interest in mammals, including human, and its application has been expanding to various fields. Recent studies further suggest that synthetic siRNA duplexes have the potential for specifically inhibiting the expression of an allele of interest without suppressing the expression of other alleles, i.e., siRNA duplexes likely confer allele-specific silencing. Such gene silencing by RNAi is an advanced technique with very promising applications. In this review, I would like to discuss the potential utility of allele-specific silencing by RNAi as a therapeutic method for dominantly inherited diseases, and describe possible improvements in siRNA duplexes for enhancing their efficacy.
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