The long term objective of this project is to develop a scalable GMP manufacturing process for the production of adeno-associated virus (AAV) vectors for the treatment of cystic fibrosis. AAV-CFTR vector constructs will be introduced into a variety of cell lines and evaluated for their ability to produce vector particles following addition of requisite packaging functions. A number of packaging constructs will be assayed in the vector-containing cell lines for their ability to efficiently direct vector particle production. Purification of transducing vector particles will be optimized by physical methods of cell lysis, gradient centrifugation, and column chromatography. AAV-CFTR vectors will be used in clinical trials for the treatment of cystic fibrosis in an attempt to correct the underlying pathophysiology of this disease. Development of this technology could lead to substantive improvements in treatment of this disease. Development of efficient methods to produce clinical grade AAV vectors could also lead to new products for the treatment of other diseases in addition to cystic fibrosis.
Development of AAV-CFTR vectors for the treatment of cystic fibrosis could result in a gene delivery 'drug' that could slow or halt disease progression. This product would serve an existing market of 30,000 affected individuals. In addition, it is envisioned that AAV vector technology would be of utility in other gene transfer applications, including treatments for other genetic diseases, cardiovascular disease, and cancer.
