Non-Primate FIV Vectors for Treatment of Hemophilia A

描述(申请人提供)：我们建议优化非灵长类猫科动物 免疫缺陷病毒(FIV)载体治疗甲型血友病 解决治疗性的构成的、长期的表达的需要 蛋白质，因子。慢病毒载体具有多种优势 基因治疗和FIV的基因传递载体具有独特的优势 其他慢病毒载体。重要的是，FIV对人类是非致病性的。FIV 载体已被证明可以在多种植物中高效表达转基因 组织和物种，包括灵长类。我们的长期目标是发展 一种商业上可行的FIV载体系统。为此，我们建议 优化体内外FIV载体技术，提高整体 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 优化了人类FVIII和FVIII的安全性、高滴度和有效性 优化的FIVIFVIII载体在小鼠体内的效果评价 血友病模型A.FIV载体系统的联合优化 体外给药本身和体内最佳给药方式的确定 预计将提高FIV载体治疗血友病A的整体效力。 媒介效力的增加转化为更低的剂量，因此风险更小。 建议的商业应用：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