Non-Primate FIV Vectors for Treatment of Hemophilia A

用于治疗甲型血友病的非灵长类 FIV 载体

• 批准号: 6444339
• 负责人: Sybille L Sauter
• 金额: $ 10万
• 依托单位: CORAUTUS GENETICS, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-21 至 2002-07-20
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6444339
• 关键词: biotechnology; coagulation factor VIII; feline immunodeficiency virus; gene delivery system; gene targeting; gene therapy; hemophilia As; laboratory mouse; technology /technique development; transfection /expression vector

DESCRIPTION (provided by applicant): We propose to optimize non-primate Feline Immunodeficiency Virus (FIV) vectors for the treatment of hemophilia A to address the need for constitutive, long-term expression of the therapeutic protein, factor VIII. Lentiviral vectors offer multiple advantages over other gene delivery vehicles for gene therapy and FIV has particular advantages over other lentiviral vectors. Importantly, FIV is non-pathogenic in humans. FIV vectors have been shown to efficiently express transgenes in a variety of tissues and species, including primates. The long-term objective is to develop a commercially feasible FIV vector system. For that purpose, we propose to optimize the FIV vector technology in vitro and in vivo to increase the overall efficiency of this gene delivery system. The specific goals are to generate the next generation FIV-based vectors optimized for safety, high titer and efficacy for delivery of human FVIII and to evaluate the in vivo efficacy of the optimized FIVIFVIII vectors in mouse models for hemophilia A. The combined optimization of the FIV vector system itself in vitro and the identification of the best mode delivery in vivo are expected to increase the overall potency of FIV vectors for hemophilia A. Increased vector potency translates into lower doses and thus fewer risks. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE

描述（由申请人提供）：我们建议优化非灵活的猫科动物 免疫缺陷病毒（FIV）载体用于治疗血友病A 满足对治疗的构成长期表达的需求 蛋白质，因子VIII。慢病毒向量提供了比其他的多个优势 基因疗法和FIV的基因输送车比 其他慢病毒载体。重要的是，FIV在人类中是非致病性的。 fiv 向量已被证明可以有效地表达各种转基因 组织和物种，包括灵长类动物。长期目标是发展 商业上可行的FIV矢量系统。为此，我们建议 在体外和体内优化FIV矢量技术以增加整体 该基因输送系统的效率。 具体目标是生成下一代基于FIV的向量 针对安全性，高滴度和疗效的人类FVIII和功效进行了优化 评估小鼠优化的Fivifviii载体的体内功效 血友病A的模型A. FIV矢量系统的组合优化 本身在体外，体内最佳模式传递的识别是 预计会增加血友病的FIV载体的总体效力。 增加的矢量效力转化为较低的剂量，因此风险较少。 拟议的商业应用程序：不可用