The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
The Mucus Barrier to Inhaled Gene Therapy
Open accessAbstract
Recent evidence suggests that the airway mucus gel layer may be impermeable to the viral and synthetic gene vectors used in past inhaled gene therapy clinical trials for diseases like cystic fibrosis. These findings support the logic that inhaled gene vectors that are incapable of penetrating the mucus barrier are unlikely to provide meaningful benefit to patients. In this review, we discuss the biochemical and biophysical features of mucus that contribute its barrier function, and how these barrier properties may be reinforced in patients with lung disease. We next review biophysical techniques used to assess the potential ability of gene vectors to penetrate airway mucus. Finally, we provide new data suggesting that fresh human airway mucus should be used to test the penetration rates of gene vectors. The physiological barrier properties of spontaneously expectorated CF sputum remained intact up to 24 hours after collection when refrigerated at 4 °C. Conversely, the barrier properties were significantly altered after freezing and thawing of sputum samples. Gene vectors capable of overcoming the airway mucus barrier hold promise as a means to provide the widespread gene transfer throughout the airway epithelium required to achieve meaningful patient outcomes in inhaled gene therapy clinical trials.
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Citations
Cites
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Effective mucus clearance is essential for respiratory health
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Self-citationSuk, J. S., Boylan, N. J., Trehan, K., Tang, B. C., Schneider, C. S., Lin, J.-M. G., Boyle, M. P., Zeitlin, P. L., Lai, S. K., Cooper, M. J., et al. (2011) · Molecular Therapy · doi:10.1038/mt.2011.160 · Cited by 94
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Cited by
Lipid-Based DNA Therapeutics: Hallmarks of Non-Viral Gene Delivery
Buck, J., Grossen, P., Cullis, P. R., Huwyler, J., & Witzigmann, D. (2019) · ACS Nano · doi:10.1021/acsnano.8b07858 · Cited by 312
Guan, S., Munder, A., Hedtfeld, S., Braubach, P., Glage, S., Zhang, L., Lienenklaus, S., Schultze, A., Hasenpusch, G., Garrels, W., et al. (2019) · Nature Nanotechnology · doi:10.1038/s41565-018-0358-x · Cited by 130
In utero gene editing for monogenic lung disease
Alapati, D., Zacharias, W. J., Hartman, H. A., Rossidis, A. C., Stratigis, J. D., Ahn, N. J., Coons, B., Zhou, S., Li, H., Singh, K., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aav8375 · Cited by 123
Tagalakis, A. D., Munye, M. M., Ivanova, R., Chen, H., Smith, C. M., Aldossary, A. M., Rosa, L. Z., Moulding, D., Barnes, J. L., Kafetzis, K. N., et al. (2018) · Thorax · doi:10.1136/thoraxjnl-2017-210670 · Cited by 61
Zhu, J., Guo, M., Cui, Y., Meng, Y., Ding, J., Zeng, W., & Zhou, W. (2022) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.1c23069 · Cited by 46
Metadata
- Authors
- Duncan, G. A., Jung, J., Hanes, J., & Suk, J. S.
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2016-12
- Volume
- 24
- Issue
- 12
- Pages
- 2043-2053
- ISSN
- 1525-0016 (ISSN-L)
- OpenAlex
- W2522111877
- Cited by
- 188
- References
- 9
- FWCI
- 10.86
- Type
- journal article
- Language
- en
- Open access
- hybrid
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
