GENE THERAPY DEVICE FOR TREATMENT OF HEMOPHILIA B

该提案的目标是开发一种新的基因治疗递送 用于治疗遗传性疾病血友病B a的装置 毁灭性和昂贵的（超过十亿美元的市场）疾病 以自发性内出血为特征。计划中的实验 将为开发细胞治疗运载工具提供第一步 用于植入动物的大血管中，并且最终， 患有这种基因缺陷的病人具体目标1计划 优化高产量、纯的人成肌细胞的分离。具体目标 2计划开发犬FIX逆转录病毒载体系统并优化 在II期临床前准备中的人成肌细胞的转导 狗试验Specific Aim 3计划优化人类 成肌细胞与已经存在的人FIX逆转录病毒载体。具体 目的4计划优化FIX转导的成肌细胞填充到中空纤维中， 纤维和FIX分泌率。成功完成这些 研究为II期在细胞中扩大这些细胞奠定了基础 包含必要数量的中空纤维的药筒，所述中空纤维包含 转导人类肌肉细胞并将该装置植入大型动物体内 模型这种方法可能是基因的关键技术 治疗行业，提供了一种安全的方法来引入植入式和 将基因产物引入系统的可回收装置 有遗传病的人的血液循环 拟议的商业应用： 这项提议是开发一种可植入的 用于通过将蛋白质递送到体循环中的装置 基因疗法治疗遗传性疾病。 该计划的重点是 治疗血友病B，一个毁灭性的和昂贵的（超过10亿美元）， 美元市场）的遗传疾病的特点是自发的内部 流血了 这种方法可能是使基因 治疗行业

The goal of this proposal is to develop a novel gene therapy delivery device for the treatment of the genetic disorder, Hemophilia B, a devastating and costly (over a billion dollar market) disease characterized by spontaneous internal bleeding. The planned experiments will provide the first steps to develop a cell therapy delivery vehicle for implantation into a large vessel of an animal, and eventually, a patient suffering from this genetic defect. Specific Aim 1 plans to optimize the isolation of high yield, pure human myoblasts. Specific Aim 2 plans to develop a canine FIX retroviral vector system and optimize transduction of human myoblasts in preparation for Phase Il preclinical dog trials. Specific Aim 3 plans to optimize the transduction of human myoblasts with an already existing human FIX retroviral vector. Specific Aim 4 plans to optimize both FIX transduced myoblast packing into hollow fibers and FIX secretion rates. The successful completion of these studies sets the stage for Phase Il to scale up these cells in a cell cartridge containing the necessary number of hollow fibers containing transduced human muscle cells and implant this device in a large animal model. This approach may be the key enabling technology for the gene therapy industry, providing a safe means to introduce an implantable and retrievable device to introduce gene products into the systemic circulation of an individual with a genetic disorder. PROPOSED COMMERCIAL APPLICATIONS: This proposal is the first step in the development of an implantable device into the systemic circulation for the delivery of proteins via gene therapy to treat genetic diseases. This plan is focused on the treatment of Hemophelia B, a devastating and costly (over a billion dollar market) genetic disease characterized by spontaneous internal bleeding. This approach could be the enabling technology for the gene therapy industry.