ΔR3-R21 ΔCT micro-dystrophin

ΔR3-R21 ΔCT micro-dystrophin (also known as Δ3849) is an experimental adeno-associated virus (AAV)-delivered gene therapy construct designed for the treatment of Duchenne muscular dystrophy (DMD). This specific construct encodes a truncated, five-repeat version of the dystrophin protein, characterized by the deletion of the R3-R21 spectrin-like repeats and the C-terminal (CT) domain. While it was designed to restore muscle membrane stability by replacing missing dystrophin, preclinical studies in D2.mdx mouse models revealed that cardiac overexpression of this particular variant accelerated the onset of dilated cardiomyopathy and heart failure, leading to premature death. Structurally, it differs from other micro-dystrophin variants by the specific deletion of hinge 3 (H3). It is primarily utilized in research to evaluate the structural requirements for functional dystrophin replacement and the potential for cardiotoxicity in gene therapy applications.

Other names

five-repeat microdystrophin construct