Genetic Modification of the Lung Directed Toward Treatment of Human Disease
Abstract
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.
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The main limitation of CF gene therapy based on delivery of a CFTR cDNA copy is the low and non-permanent CFTR expression obtained in the affected tissues.
“The main limitation of this gene therapy strategy is the low and non-permanent CFTR expression obtained in the affected tissues7,53.”
From Allele specific repair of splicing mutations in cystic fibrosis through AsCas12a genome editing (2019) · cites this paper as [53]
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- Authors
- Sondhi, D., Stiles, K. M., De, B. P., & Crystal, R. G.
- Affiliations
- Weill Cornell Medicine (US)
- Venue
- Human Gene Therapy
- Publisher
- SAGE Publications
- Published
- 2017-01
- Volume
- 28
- Issue
- 1
- Pages
- 3-84
- ISSN
- 1043-0342 (ISSN-L)
- 1557-7422
- OpenAlex
- W2582514264
- Cited by
- 36
- References
- 609
- Citations by year
- 2026: 1 · 2023: 3 · 2022: 7 · 2021: 4 · 2020: 9 · 2019: 2 · 2018: 6 · 2017: 4
- FWCI
- 0.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Gene Therapy (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Keywords
- pulmonary gene therapy, viral vectors, non-viral vectors, cystic fibrosis, alpha-1 antitrypsin deficiency, asthma, allergy, lung cancer, respiratory syncytial virus, Pseudomonas infection, pulmonary arterial hypertension, graft rejection, lung injury, persistent gene expression, cell targeting
- MeSH terms
- Animals, Genetic Vectors, Humans, Lung Diseases, Viruses, Genetic Therapy
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