DEVELOPMENT OF AN AAV CFTR VECTOR PRODUCTION SYSTEM

提出的研究旨在开发大规模的电池工艺

The proposed research is intended to develop a large scale cell process and purification system for the production of recombinant AAV-CFTR vector. A suspension adapted packaging cell line will be constructed. This cell line will be used to develop a large scale batch suspension process utilizing a temperature-sensitive adenovirus mutant for bulk vector production. Vector recovery and purification methods will be optimized for large scale clinical manufacture. Formulation and drug delivery development will be initiated with purified vector. Clinical production of large quantities of AAV-CHR vector will be required for mid- and late-stage trials in patients with cystic fibrosis. Development of efficient and large scale methods to produce AAV vectors could also lead to new products for the treatment of other diseases in addition to cystic fibrosis. PROPOSED COMMERCIAL APPLICATION: 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, this AAV vector production technology would be of utility in other gene transfer applications, including treatment of genetic disease, cardiovascular disease, and cancer.