ADENOVIRUS SF TRANSDUCTION FOR ANGIOGENIC GENE THERAPY

肝细胞生长因子分散因子(SF/HGF)是一种多效性细胞因子，在体内外具有显著的血管生成活性，可作为治疗性血管生成的候选因子，即在动脉粥样硬化损伤区域应用生长因子刺激新生血管。第一阶段项目将评估在大鼠急性心肌和外周缺血模型中腺病毒载体中使用SF/HGF进行血管生成基因治疗的可行性。其具体目的是1)鉴定和优化含有SF/HGF编码序列的腺病毒载体用于基因转移实验；2)测试直接注射这些载体是否导致SF/HGF表达，这种表达是否定位，以及是否针对缺血组织；以及3)确定SF/HGF转导是否在体内诱导血管生成。第一阶段研究的成功完成将导致在第二阶段对更大的慢性心肌和外周缺血动物模型进行验证性实验，这将为IND申报和SF/HGF基因治疗的临床研究奠定基础。拟议的商业应用：第一阶段和第二阶段项目旨在提供关键的临床前数据，以支持SF/HGF基因疗法临床试验的监管申报和午餐。Angion Biomedica公司与北岸大学医院签署了一项技术转让协议，其中包括对美国患者5837676的独家许可，即“使用分散因子增强血管生成”。该公司希望与制药行业合作伙伴合作，进行SF/HGF基因疗法的临床开发和商业化，以治疗冠状动脉疾病和外周血管疾病。心血管疾病是美国发病率和死亡率的主要原因，也是医疗保健市场的最大部分。

Scatter factor of hepatocyte growth factor (SF/HGF) is pleiotropic cytokine that has significant angiogenic activity in vitro and in vivo, and may be a good candidate for therapeutic angiogenesis, i.e. administration of growth factors to stimulate neovascularization in areas of atherosclerotic damage. The Phase I project will evaluate the feasibility of angiogenic gene therapy with SF/HGF in an adenoviral vector in rat models of acute myocardial and peripheral ischemia. The specific aims are 1) to characterize and optimize adenoviral vectors containing SF/HGF coding sequences for use in gene transfer experiments; 2) to test whether direct injection of these vectors results in SF/HGF expression, whether this expression is localized, and whether it is specific for ischemic tissue; and 3) to determine if SF/HGF transduction induces angiogenesis in vivo. Successful completion of the Phase I studies will lead to confirmatory experiments in larger animal models of chronic myocardial and peripheral ischemia in Phase II that will be the basis for a IND filing and clinical studies of SF/HGF gene therapy. PROPOSED COMMERCIAL APPLICATIONS: The Phase I and Phase II projects are designed to provide the key pre- clinical data to support regulatory filing and lunch of clinical trials of SF/HGF gene therapy. Angion Biomedica Corp. has signed a technology transfer agreement with North Shore University Hospital that includes an exclusive licence for US Patient 5837676, "Use of Scatter Factor to Enhance Angiogenesis". The company expects to pursue clinical development and commercialization of SF/HGF gene therapy to treat coronary artery disease and peripheral vascular disease in collaboration with a pharmaceutical industry partner. Cardiovascular disease is the leading cause of morbidity and mortality in the US and the largest segment of the health care market.