Abstract:
Rett Syndrome (RTT) is a rare neuronal disorder caused by alteration of MECP2 gene. There is currently no cure for RTT, but gene therapy with adeno-associated virus (AAV) vectors holds great promise as a potential treatment option. AAV vectors have shown excellent safety and efficacy profiles in preclinical studies and clinical trials for a variety of diseases. However, systemic delivery of AAV vectors to achieve widespread gene transfer to the brain is challenging due to the limited ability of AAV to cross the bloodbrain barrier and the potential for peripheral toxicity. In this context, the development of AAV vectors with improved brain penetrance and sub-toxic levels of transgene expression is critical. Several modifications to AAV vectors have been tested in preclinical studies for RTT, including the use of alternative promoters, 3’ UTRs, and capsids, resulting in improved control of MeCP2 expression and reduced peripheral toxicity. Further studies are needed to determine the optimal AAV vector design and delivery strategy for RTT gene therapy. Nonetheless, AAV gene therapy holds great promise for the treatment of RTT, and ongoing research in this field may pave the way for a much-needed cure for this debilitating disorder.
