Despite the unprecedented beneficial effects of rAAV gene therapy in animal models of
Duchenne muscular dystrophy (DMD), the need to inject large amounts of vector in vivo to improve
phenotype raises obvious biosafety concerns. While rAAV vectors generally exhibit a good safety profile,
specific pathological phenotypes such as those observed in dystrophin-deficient muscles may
promote immunotoxic/genotoxic effects. Increasing the therapeutic index of rAAV in DMD muscles
by reducing the effective dose could be a pivotal means of ensuring efficient clinical translation. This
requires a comprehensive understanding of the rAAV transduction process, which is almost always
studied in non-pathological tissues or in vitro. In this review, we focus on the molecular fate of rAAV
after injection, and how the individual stages of transduction could be affected in the context of DMD.
Keywords: Muscle, Duchenne muscular dystrophy, Adeno-associated virus, Gene therapy, Restriction factors, In vivo.
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