Use of split intein and myotropic AAV vectors enables effective preclinical gene therapy for dysferlinopathy.

Split-intein and myotropic AAV vectors enable full-length dysferlin expression and functional recovery in an LGMDR2 mouse model, surpassing previous strategies.

• Why it matters: LGMDR2 is caused by mutations in the DYSF gene, leading to muscle weakness due to lack of dysferlin, and effective gene delivery is limited by the large size of the dysferlin cDNA exceeding AAV capacity.
• What they did: Researchers used split-intein technology combined with myotropic AAV vectors to reconstitute full-length dysferlin, validating the approach in vitro and in vivo with systemic delivery in mice, comparing it to homologous recombination strategies.
• The result: The approach improved muscle strength, contractile force, and reduced tissue abnormalities at both early and late disease stages, demonstrating greater efficiency and potential for curative gene therapy for LGMDR2.