GENE DELIVERY SYSTEMS FOR BRONCHO-ALVEOLAR DISEASES

健康大龄儿童呼吸道合胞病毒感染的研究 成人通常局限于上呼吸道。在……里面 然而，某些疾病人群(患有慢性疾病的老年患者 心肺疾病、成人慢性白血病)、呼吸道合胞病毒可引起 危及生命的下呼吸道疾病。我们展示了细胞 体外转染人AAT基因的表达载体 抵抗呼吸道合胞病毒感染。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，这个项目的具体目标是开发一种AAT基因 吸入给药预防呼吸道合胞病毒的药物 感染。AAT基因药物的目标人群将是 包括在RSV季节期间的上述患者。此外，这样的 一种产品，如果在儿童中被证明是安全有效的，很可能是 对患有支气管肺发育不良的儿童人群的好处或 先天性心脏病。炎症是一个重要的组成部分 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。可获得的数据 强烈建议AAT基因的传递使其得以表达 在肺上皮细胞中会导致抗蛋白分解和抗- 炎症活动。因此，AAT基因药物的使用可能 合理地扩展到这些适应症。 建议的商业应用： AAT基因药物可能是一种抗蛋白水解物和抗病毒药物。 下列肺部疾病中的炎性因子：呼吸道合胞病毒感染， 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.