Figure 3. RNAi for Isoform- and Allele-Specific Silencing.

(A) Isoform-specific RNAi to target disease-associated isoforms in cancer. VEGF₁₆₅ isoform overexpression is implicated in tumour angiogenesis. Targeting of the VEGF transcript with siRNA targeted to the exon 5/7 boundaries, in association with RISC, induces specific VEGF₁₆₅ knockdown, while having no effect on other VEGF isoforms, e.g., VEGF₁₈₉.

(B) Allele-specific RNAi in the autosomal dominant slow channel congenital myasthenic syndrome. A missense mutation (red bar) in the muscle acetylcholine α-subunit (αS226F) induces a C→U change in the mutant allele. Use of siRNA specific for the αS226F mutation (A binding to U), induces discriminatory silencing of the mutant transcript, leaving the wild-type transcript mostly unaffected.