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 gene therapy, significantly improving muscle function in an LGMDR2 mouse model.

• Why it matters: LGMDR2 is caused by mutations in the DYSF gene, and delivering the large dysferlin cDNA exceeds current AAV capacity, hindering effective gene therapy.
• What they did: Researchers developed a split-intein version of dysferlin and used systemic AAV delivery to reconstitute full-length protein in mice, validating its ability to restore membrane repair and muscle strength.
• The result: This approach outperformed homologous recombination strategies, leading to greater functional recovery and highlighting its potential as a curative treatment for dysferlinopathy.