GENE THERAPY DEVICE FOR TREATMENT OF HEMOPHILIA B

这项提议的目标是开发一种新的基因治疗方法。 治疗遗传性疾病的设备，血友病B，a 毁灭性且代价高昂(市场价值超过10亿美元)的疾病 以自发性内出血为特征的。计划中的实验 将为开发细胞治疗运载工具提供第一步 移植到动物的大容器中，最终， 患有这种遗传缺陷的病人。特定目标1计划 优化分离高产量、纯净的人成肌细胞。特定目标 2计划开发犬固定逆转录病毒载体系统并优化 人成肌细胞在Il期临床前准备中的转导 狗的试验。特定目标3计划优化人类基因转导 已经存在的人类FIX逆转录病毒载体的成肌细胞。特定的 Aim 4计划优化两种固定转导成肌细胞填充到中空 纤维和固定分泌率。这些项目的顺利完成 研究为Il期扩大细胞中的这些细胞奠定了基础 包含所需数量的中空纤维的盒，其中包含 转导人类肌肉细胞，并将该装置植入大型动物体内 模特。这种方法可能是基因的关键使能技术 治疗行业，提供一种安全的手段来引入可植入和 可回收的装置，将基因产品引入系统 遗传性疾病的个体的循环。 建议的商业应用： 这项提议是开发植入物的第一步 进入体循环的装置，通过 基因疗法用于治疗遗传性疾病。这项计划的重点是 治疗乙型血吸虫病，一种破坏性的和昂贵的(超过10亿) 美元市场)遗传病，其特征是自发性的内部 在流血。这种方法可能是基因的使能技术 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.