Gene Silencing

Gene silencing encompasses different means to reduce the expression of a gene. The research in Gao lab focuses on effective ways to achieve CNS specific therapeutic gene expression, avoiding treatment of unintended tissues. This work allows the AAV based CNS gene therapy to be safer and reduces potential immune responses. This also included the improvement of rAAV gene silencing constructs to increase genome integrity and efficacy. As our current study points out, shRNA-encoding sequences compromise the integrity of rAAV genome. Optimization of current rAAV-shRNA design to improve RNAi efficacy and minimize the potential side effects of truncated genomes are in demand. In addition, we are developing tissue-specific and inducible rAAV gene silencing constructs for the treatment of gain-of-function genetic disease, such as Amyotrophic lateral sclerosis (ALS) or Alexander disease (AD).