Allele-specific RNAi selectively silences mutant SOD1 and achieves significant therapeutic benefit in vivo

RNA interference (RNAi) has the potential to treat diseases caused by dominant, gain-of-function type of gene mutations. In these diseases, one allele is mutated and produces a toxic protein, whereas the other allele is normal and performs vital functions. One challenge in the treatment is to specifically inhibit the mutant allele toxicity while maintaining the normal allele function. To test allele-specific silencing in vivo, we made transgenic...