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Small interfering RNA (siRNA) represses a specific target gene that has a perfectly complementary sequence by a pathway referred to as RNA interference (RNAi). Researchers have successfully diverted this natural pathway to artificially knockdown intended genes. RNAi shows promise for therapeutic applications to human diseases (Castanotto and Rossi, 2009; Ketting, 2011). Over the past decade, more than twenty siRNAs have been applied to clinical trials for dozens of diseases, including various cancers, viral infections, and genetic disorders (Davidson and McCray, 2011; Snead and Rossi, 2012). Ongoing patient trials are expected to yield success. However, several major problems, such as the efficacy and off-target effect of siRNA, remain to be overcome before RNAi-based therapeutics can be efficiently introduced into clinical practice. In the present paper, I propose a procedure for selecting sequences of highly functional siRNAs with few off-target effects.

Optimal choice of functional and off-target effect-reduced siRNAs for RNAi therapeutics