Journal article
Viral Vectors, Animal Models, and Cellular Targets for Gene Therapy of Cystic Fibrosis Lung Disease
Human gene therapy, Vol.31(9-10), pp.524-537
05/01/2020
DOI: 10.1089/hum.2020.013
PMCID: PMC7232698
PMID: 32138545
Abstract
After more than two decades since clinical trials tested the first use of recombinant adeno-associated virus (rAAV) to treat cystic fibrosis (CF) lung disease, gene therapy for this disorder has undergone a tremendous resurgence. Fueling this enthusiasm has been an enhanced understanding of rAAV transduction biology and cellular processes that limit transduction of airway epithelia, the development of new rAAV serotypes and other vector systems with high-level tropism for airway epithelial cells, an improved understanding of CF lung pathogenesis and the cellular targets for gene therapy, and the development of new animal models that reproduce the human CF disease phenotype. These advances have created a preclinical path for both assessing the efficacy of gene therapies in the CF lung and interrogating the target cell types in the lung required for complementation of the CF disease state. Lessons learned from early gene therapy attempts with rAAV in the CF lung have guided thinking for the testing of next-generation vector systems. Although unknown questions still remain regarding the cellular targets in the lung that are required or sufficient to complement CF lung disease, the field is now well positioned to tackle these challenges. This review will highlight the role that next-generation CF animal models are playing in the preclinical development of gene therapies for CF lung disease and the knowledge gaps in disease pathophysiology that these models are attempting to fill.
Details
- Title: Subtitle
- Viral Vectors, Animal Models, and Cellular Targets for Gene Therapy of Cystic Fibrosis Lung Disease
- Creators
- Yinghua Tang - University of IowaZiying Yan - University of IowaJohn F. Engelhardt - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- Human gene therapy, Vol.31(9-10), pp.524-537
- Publisher
- Mary Ann Liebert, Inc., publishers
- DOI
- 10.1089/hum.2020.013
- PMID
- 32138545
- PMCID
- PMC7232698
- ISSN
- 1043-0342
- eISSN
- 1557-7422
- Language
- English
- Date published
- 05/01/2020
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984284356302771
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