AAV Viral Vector Designs For Therapeutic Application

Recombinant Adeno-associated viral vectors (AAV) has emerged as the most preferred gene delivery modality for long term therapy. A key component of successful gene therapy is the design of the vector. The vector design has two primary components; A) the transgene design with sequence variations and regulatory elements; B) the AAV capsid. These two elements of vector design are critical for the expression efficacy, safety and specificity of the AAV mediated gene therapy. In terms of the therapeutic gene of choice, a single AAV virion can only carry about 4.7KB of cargo DNA, therefore, for large genes, dual AAV vector designs are a necessity. We have developed several unique methods of split gene approaches to accommodate large therapeutic genes including the hybrid dual-AAV vector system. Additionally, the tissue-specific promotors allow for targeted expression of the transgene in the disease tissues. Transgene organization can be optimized for maximal expression and safety during the vector production process. Finally, selection of the appropriate AAV capsid serotype allows for high level expression in the disease affected tissues preferentially.