Design of AAV Vectors for Delivery of Large or Multiple Transgenes

Adeno-associated virus (AAV)-mediated gene therapy has evolved from bench to bedside, and now is the therapy of choice for certain inherited diseases. However, the small packaging capacity of AAV vectors prevents this technique from treating genetic diseases with mutations of large genes. Multiple strategies, including split AAV gene delivery and oversized AAV gene delivery, have been explored to deliver large gene expression cassettes. These strategies have gained some success in animal experiments. In this chapter, we review the progress of AAV-mediated delivery of large expression cassettes. We also review using AAV to deliver multiple transgenes.