Recombinant adeno-associated virus: formulation challenges and strategies for a gene therapy vector

Recombinant adeno-associated virus (AAV)-based vectors capable of expressing therapeutic gene products in vivo have shown significant promise for human gene therapy. One challenge facing the field is the development of vector formulations to achieve optimal vector safety, stability and efficacy. Formulation challenges for AAV vectors can be divided into those relating to maintaining vector activity during purification and storage, and those relating to efficient target tissue transduction in vivo. AAV vectors are potentially susceptible to loss of activity through aggregation, proteolysis and oxidation, as well as through non-specific binding to product contact materials used for vector purification and storage. These deleterious changes need to be thoroughly characterized, and the conditions and excipients to prevent them need to be identified. For in vivo administration, major vector formulation challenges include optimization of efficiency and specificity of target tissue transduction, and the ability to overcome host immune responses.