Genetic Modification of the Lung Directed Toward Treatment of Human Disease

• Published in: Human gene therapy Vol. 28; no. 1; p. 3
• Main Authors: Sondhi, Dolan, Stiles, Katie M, De, Bishnu P, Crystal, Ronald G
• Format: Journal Article
• Language: English
• Published: United States 01.01.2017
• Subjects: Animals; Genetic Therapy; Genetic Vectors - administration & dosage; Humans; Lung Diseases - genetics; Lung Diseases - therapy; Viruses - genetics; lung; gene therapy; lung disease; non-viral vectors; viral vectors
• ISSN: 1557-7422
• 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.