GENE DELIVERY SYSTEMS FOR BRONCHO-ALVEOLAR DISEASES

健康大龄儿童呼吸道合胞病毒（RSV）感染 而成人通常局限于上呼吸道。 在 然而，某些疾病人群（患有慢性 心肺疾病，慢性白血病成人），RSV可引起 危及生命的下呼吸道疾病。 我们发现细胞 用编码人AAT的质粒体外转染， 抗RSV感染。 我们推断细胞内的AAT 抑制RSV F蛋白的成熟，从而抑制感染性。 因此，该计划的具体目标是开发AAT基因， 预防呼吸道合胞病毒的吸入给药药物 感染 AAT基因药物的目标人群将 包括RSV季节期间的上述患者。 此外，这种 一种产品，如果被证明对儿童安全有效， 有益于支气管肺发育不良的儿科人群，或 先天性心脏病 炎症是一个重要组成部分， 许多肺部疾病包括肺气肿、囊性纤维化、哮喘 特发性肺纤维化和急性肺损伤。 现有数据 强烈表明AAT基因递送使得其表达 在肺上皮细胞中会产生抗蛋白水解和抗 炎症活动。 因此，AAT基因药物的使用可能是 合理地扩展到这些迹象。 拟定商业应用： AAT基因药物可作为一种抗蛋白水解和抗 在以下肺部疾病中的炎性因子：RSV感染， 肺气肿，囊性纤维化，特发性肺纤维化，急性肺 受伤和哮喘。

Respiratory Syncytial Virus (RSV) infection in healthy older children and adults is usually localized to the upper respiratory tract. In certain disease populations, however (elderly patients with chronic cardiopulmonary disease, adults with chronic leukemia), RSV can cause life-threatening lower respiratory tract disease. We showed that cells transfected in vitro with a plasmid encoding for human AAT were resistant to infection with RSV. We reason that intracellular AAT inhibited maturation of RSV F protein and thus inhibited infectivity. The specific aim of this program, therefore, is to develop an AAT gene medicine, administered by inhalation, for the prevention of RSV infection. The target population for the AAT gene medicine would include the above-listed patients during the RSV season. Further, such a product, if shown safe and effective in children would likely be of benefit to pediatric populations with bronchopulmonary dysplasia or congenital heart disease. Inflammation is a significant component of many lung diseases including emphysema, cystic fibrosis, asthma, idiopathic pulmonary fibrosis and acute lung injury. The available data strongly suggest that delivery of the AAT gene so that it is expressed in lung epithelial cells would result in both antiproteolytic and anti- inflammatory activities. The use of AAT gene medicine could thus be rationally extended to these indications. PROPOSED COMMERCIAL APPLICATION: AAT gene medicine could be indicated as an anti-proteolytic and anti- inflammatory agent in the following lung diseases: RSV infection, emphysema, cystic fibrosis, idiopathic pulmonary fibrosis, acute lung injury and asthma.