ADENOVIRUS SF TRANSDUCTION FOR ANGIOGENIC GENE THERAPY

肝细胞生长因子分散因子（SF/HGF）是一种多效细胞因子，在体内外均具有显著的促血管生成活性，有望成为治疗性血管生成（即给予生长因子以刺激动脉粥样硬化损伤区域的新生血管形成）的良好候选者。I期项目将评估在急性心肌和外周缺血大鼠模型中使用腺病毒载体中的SF/HGF进行血管生成基因治疗的可行性。具体目的是1）表征和优化用于基因转移实验的含有SF/HGF编码序列的腺病毒载体; 2）测试这些载体的直接注射是否导致SF/HGF表达，这种表达是否是局部的，以及它是否对缺血组织特异;和3）确定SF/HGF转导是否诱导体内血管生成。I期研究的成功完成将导致在II期中在慢性心肌和外周缺血的较大动物模型中进行验证性实验，这将是SF/HGF基因治疗的IND申请和临床研究的基础。拟议的商业应用：I期和II期项目旨在提供关键的临床前数据，以支持SF/HGF基因治疗临床试验的监管备案和午餐。Angion生物医学公司与北岸大学医院签署了一项技术转让协议，其中包括美国患者5837676的独家许可证，“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.