Gene therapy’s other immune toxicity problem

The AAV gene therapy world is still unraveling the modality’s toxicities caused by capsid-directed immune responses, but DMD trials have resurfaced a different immune-related toxicity that developers need to put back on their radar. In a positive sign for industry’s ability to solve shared problems, competitors are pooling their heads together to solve this issue and pre-empt future occurrences.

Transgene-directed cellular immunity — a risk that was all but forgotten when adeno-associated viral (AAV) vectors replaced adenoviral vectors more than 20 years ago — is the likely culprit behind five severe muscle weakness events across trials of three different Duchenne muscular dystrophy (DMD) gene therapies over the past year...