Gene therapy is finally teetering on the edge of becoming a drug development mainstay, with at least nine AAV-based therapies in Phase III or II/III testing. An analysis of the AAV therapies in the clinic reveals a growing diversity of vector subtypes being used in vivo, engineering strategies gaining traction, and an expansion of the modality beyond monogenic diseases.
The 2017 approval of Luxturna voretigene neparvovec-rzyl from Spark Therapeutics Inc. as the first in vivo gene therapy broke the modality’s twenty-year logjam.
Now, over 70 gene therapies are in proof-of-concept or pivotal trials, which will answer whether the modality can deliver on its promise.
Like Luxturna, many of them deliver therapeutic genes via adeno-associated viral (AAV) vectors, due to the vectors’ ability to infect non-dividing cells and their comparative safety. AAVs integrate into a specific site