AAVantgarde Bio has two proprietary, AAV-based large gene delivery platforms. The first leveraging DNA recombination, named dual hybrid; and the second, a protein trans-splicing, named AAV intein. The company is validating the platforms in two lead programs: Usher Syndrome Type 1 B associated retinitis pigmentosa (Usher1B), using dual hybrid; and Stargardt disease, using AAV intein.
AAV gene therapy has been limited by transgene capacity, and the Company’s platforms enable delivery of large genes to tissue and cells in vivo; something that could extend into many disease areas.
Usher syndrome type 1B (Usher1B) is an inherited disease that affects the retina and the inner ear. Usher1B is caused by mutations in the MYO7A gene. The therapeutic gene to treat Usher1B is 6.7 kb long and is therefore too large to fit inside a standard AAV vector. Approximately 20,000 patients in the U.S. and E.U. have Usher1B. These children are born deaf, have vestibular dysfunction, and begin to progressively lose vision in their first decade of life. Although, there are surgical treatments available to treat deafness in these patients, there are no treatments available to treat progressive vision loss and blindness in these patients.
Stargardt disease is the most common inherited macular degeneration. Inherited in most of the cases as autosomal recessive, Stargardt disease is caused by mutations in the ABCA4 gene. The therapeutic gene to treat Stargardt disease (ABCA4) is 6.8 kb long which is too large to fit inside a standard AAV vector. Stargardt disease affects approximately 60,000-75,000 patients in the U.S. and E.U. Currently there are no treatments for the blindness caused by Stargardt disease.