Non-immunogenic utrophin gene therapy for the treatment of muscular dystrophy animal models.

ABSTRACT: The essential product of the Duchenne muscular dystrophy (DMD) gene is dystrophin¹, a rod-like protein² that protects striated myocytes from contraction-induced injury^3,4. Dystrophin-related protein (or utrophin) retains most of the structural and protein binding elements of dystrophin⁵. Importantly, normal thymic expression in DMD patients⁶ should protect utrophin by central immunologic tolerance. We designed a codon-optimized, synthetic transgene encoding a miniaturized utrophin (µUtro), deliverable by adeno-associated virus (AAV) vectors. Here, we show that µUtro is a highly functional, non-immunogenic substitute for dystrophin, preventing the most deleterious histological and physiological aspects of muscular dystrophy in small and

SUBMITTER: Song Y 

PROVIDER: S-EPMC7274039 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature