Sondhi Dolan, Stiles Katie M, De Bishnu P, Crystal Ronald G
Department of Genetic Medicine, Weill Cornell Medical College , New York, New York.
Hum Gene Ther. 2017 Jan;28(1):3-84. doi: 10.1089/hum.2016.152.
Genetic modification therapy is a promising therapeutic strategy for many diseases of the lung intractable to other treatments. Lung gene therapy has been the subject of numerous preclinical animal experiments and human clinical trials, for targets including genetic diseases such as cystic fibrosis and α1-antitrypsin deficiency, complex disorders such as asthma, allergy, and lung cancer, infections such as respiratory syncytial virus (RSV) and Pseudomonas, as well as pulmonary arterial hypertension, transplant rejection, and lung injury. A variety of viral and non-viral vectors have been employed to overcome the many physical barriers to gene transfer imposed by lung anatomy and natural defenses. Beyond the treatment of lung diseases, the lung has the potential to be used as a metabolic factory for generating proteins for delivery to the circulation for treatment of systemic diseases. Although much has been learned through a myriad of experiments about the development of genetic modification of the lung, more work is still needed to improve the delivery vehicles and to overcome challenges such as entry barriers, persistent expression, specific cell targeting, and circumventing host anti-vector responses.
基因修饰疗法是一种很有前景的治疗策略，适用于许多其他治疗方法难以治愈的肺部疾病。肺部基因治疗一直是众多临床前动物实验和人体临床试验的主题，其治疗靶点包括囊性纤维化和α1抗胰蛋白酶缺乏症等遗传性疾病、哮喘、过敏和肺癌等复杂疾病、呼吸道合胞病毒（RSV）和铜绿假单胞菌等感染，以及肺动脉高压、移植排斥反应和肺损伤。人们采用了多种病毒和非病毒载体来克服肺部解剖结构和天然防御机制对基因转移造成的诸多物理障碍。除了治疗肺部疾病，肺还有潜力被用作一个代谢工厂，生产蛋白质并释放到循环系统中，用于治疗全身性疾病。尽管通过大量实验已经对肺部基因修饰的发展有了很多了解，但仍需要开展更多工作来改进递送载体，并克服诸如进入障碍、持续表达、特异性细胞靶向以及规避宿主抗载体反应等挑战。
