DEVELOPMENT OF AN AAV CFTR VECTOR PRODUCTION SYSTEM

该研究旨在开发一种大规模的电池工艺 用于生产重组AAV-CFTR的纯化系统 vector.将构建悬浮适应的包装细胞系。 该细胞系将用于开发大规模批次混悬液 利用温度敏感性腺病毒突变体进行批量生产的方法 载体生产载体回收和纯化方法将在 优化用于大规模临床生产。配方和药物 将用纯化的载体启动递送开发。临床 将需要生产大量的AAV-CMV载体， 囊性纤维化患者的中期和晚期试验。发展 有效和大规模的方法来生产AAV载体也可以 导致新产品用于治疗其他疾病，除了 囊性纤维化 拟议的商业应用：开发AAV-CFTR载体， 囊性纤维化的治疗可以产生一种基因递送“药物”， 可以减缓或阻止疾病的进展。该产品将服务于 现有市场3万人。此外，该AAV 载体生产技术在其它基因转移中也是有用的 应用，包括治疗遗传性疾病、心血管疾病 疾病和癌症。

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.