Two Viruses, One Protein: A Gene Therapy for Dysferlinopathy

Jeff's Daily Pick. The gene that fails in dysferlinopathy is too big for a gene therapy virus. So researchers split it across two viruses that stitch the protein back together inside muscle.

In the United States, investigators at the University of Washington and Children's National Hospital published preclinical data in Science Translational Medicine on October 7, 2026 supporting KNA-155, Kinea Bio's gene therapy for dysferlinopathy, a form of limb girdle muscular dystrophy known as LGMDR2 or LGMD2B. Kinea highlighted the paper on October 15. The corresponding author, Hichem Tasfaout, sits on Kinea's scientific advisory board, and several authors co founded the company.

The size problem

Adeno associated virus, the standard vehicle for muscle gene therapy, carries about 4.7 kilobases. The dysferlin coding sequence is roughly 6.2 kilobases, and the protein must be full length to work. The published approach splits the sequence across two AAV vectors and uses split inteins, protein segments that splice themselves together, to reconstitute complete dysferlin inside the muscle cell. Delivery uses a capsid designed to target muscle, AAV SLB101, licensed from Solid Biosciences in September 2025.

The results in animals

The highest dose tested was 10 times lower than doses commonly used with conventional AAV serotypes, and about 5 times lower than an earlier dual AAV strategy that relies on DNA recombination. Against that earlier method, the split intein approach produced more full length dysferlin and greater functional improvement. Treatment improved contractile force and reduced fibrosis and fatty degeneration, both when given near disease onset and in models with established, advanced disease, according to the company.

Dose is the reason this matters. High AAV doses have been behind liver damage and immune reactions that halted programs across the field, and they drive manufacturing cost. Kinea says the Jain Foundation's $1.1 million investment, announced in September 2025, funds dose finding and GLP toxicology studies needed before an IND. People with dysferlinopathy are usually diagnosed years after symptoms start, which is why the advanced disease result is the one to watch in a first trial.