Review

Gene Therapy (2006) 13, 509–516. doi:10.1038/sj.gt.3302726; published online 16 February 2006

Target selectivity in mRNA silencing

N Aronin1

1University of Massachusetts, Worcester, MA, USA

Correspondence: Professor N Aronin, University of Massachusetts, 55 Lake Avenue North, Worcester, MA 1655, USA. E-mail: Aronin@umassmed.edu

Received 1 December 2005; Revised 21 December 2005; Accepted 5 January 2006; Published online 16 February 2006.

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Abstract

Despite the excitement and promise of RNA interference in treating neurodegenerative disease, disease gene mRNA might resist mRNA silencing. Conventional siRNA design does not uniformly distinguish a mutant from a wild-type allele. CAG expansions in trinucleotide repeat diseases are unselective targets for small siRNAs. This review will consider recent discoveries in mechanisms of RNA interference and siRNA modifications that improve siRNA selectivity, delivery and performance.

Keywords:

siRNA, single nucleotide polymorphisms, RISC assembly, Huntington's disease

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