Non-Primate FIV Vectors for Treatment of Hemophilia A

描述（由申请人提供）：我们建议优化非灵长类猫科动物 用于治疗血友病A的免疫缺陷病毒（FIV）载体， 解决了对治疗药物的组成性长期表达的需要， 蛋白质，因子VIII。慢病毒载体相对于其他载体具有多种优势。 用于基因治疗和FIV的基因递送载体具有特别的优点， 其他慢病毒载体。重要的是，FIV在人类中是非致病性的。FIV 载体已显示在多种细胞中有效表达转基因， 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载体系统。为此，我们建议 优化FIV载体技术在体外和体内，以增加整体 这种基因传递系统的效率。 具体目标是生成下一代基于FIV的载体 针对安全性、高滴度和递送人FVIII的有效性进行了优化， 为了评价优化的FIVIFVIII载体在小鼠中的体内功效， 血友病A的模型。FIV矢量系统的组合优化 本身在体外和最佳模式在体内递送的鉴定是 预期增加FIV载体对血友病A的总体效力。 载体效力的增加转化为较低的剂量，从而降低风险。 拟定商业应用：不可用

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