Profiling of mismatch discrimination in RNAi enabled rational design of allele-specific siRNAs.

ABSTRACT: Silencing specificity is a critical issue in the therapeutic applications of siRNA, particularly in the treatment of single nucleotide polymorphism (SNP) diseases where discrimination against single nucleotide variation is demanded. However, no generally applicable guidelines are available for the design of such allele-specific siRNAs. In this paper, the issue was approached by using a reporter-based assay. With a panel of 20 siRNAs and 240 variously mismatched target reporters, we first demonstrated that the mismatches were discriminated in a position-dependent order, which was however independent of their sequence contexts using position 4th, 12th and 17th as examples. A general model was further built for mismatch discrimination at all positions using 230 additional reporter constructs

SUBMITTER: Huang H 

PROVIDER: S-EPMC2794185 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature