Advancements in AAV vector optimization for DMD gene therapy
Duchenne muscular dystrophy(DMD)is a progressive muscle wasting disease caused by mutations in the gene encoding dystrophin,which prevents the body from producing functional dystrophin protein.Ultimately,respiratory or cardiac failure leads to early mortality in adulthood.Systemic gene therapy represents the most effective approach for treating DMD to the fullest extent.Adeno-associated virus(AAV)vectors are highly promising gene therapy vehicles and have achieved unprecedented clinical success in the treatment of various genetic disorders.However,AAV vector-based gene therapy for DMD still faces significant challenges,including the inability to accommodate the full-length dystrophin coding sequence,inadequate muscle targeting with substantial liver sequestration,substantial degradation and reduced transduction efficiency in vivo,immune responses against AAV capsid proteins,difficulties in large-scale AAV production,and safety concerns.Optimization of AAV vectors aims to utilize genetic engineering techniques to modify its relevant properties to tailor the optimal vector for DMD gene therapy.This review summarizes the directions and strategies for optimizing AAV vectors to overcome the barriers of DMD gene therapy.
NETL
NSTL
万方数据
维普
