Journal article
Identification of AAV serotypes for lung gene therapy in human embryonic stem cell-derived lung organoids
- Abstract:
- <jats:title>Abstract</jats:title> <jats:p>Gene therapy is being investigated for a range of serious lung diseases, such as cystic fibrosis and emphysema. Recombinant adeno-associated virus (rAAV) is a well-established, safe, viral vector for gene delivery with multiple naturally occurring and artificial serotypes available displaying alternate cell, tissue, and species-specific tropisms. Efficient AAV serotypes for the transduction of the conducting airways have been identified for several species; however, efficient serotypes for human lung parenchyma have not yet been identified. Here, we screened the ability of multiple AAV serotypes to transduce lung bud organoids (LBOs)—a model of human lung parenchyma generated from human embryonic stem cells. Microinjection of LBOs allowed us to model transduction from the luminal surface, similar to dosing via vector inhalation. We identified the naturally occurring rAAV2 and rAAV6 serotypes, along with synthetic rAAV6 variants, as having tropism for the human lung parenchyma. Positive staining of LBOs for surfactant proteins B and C confirmed distal lung identity and suggested the suitability of these vectors for the transduction of alveolar type II cells. Our findings establish LBOs as a new model for pulmonary gene therapy and stress the relevance of LBOs as a viral infection model of the lung parenchyma as relevant in SARS-CoV-2 research<jats:italic>.</jats:italic></jats:p>
- Publication status:
- Published
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(Preview, Version of record, 4.2MB, Terms of use)
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- Publisher copy:
- 10.1186/s13287-020-01950-x
Authors
- Publisher:
- BioMed Central
- Journal:
- Stem Cell Research and Therapy More from this journal
- Volume:
- 11
- Issue:
- 1
- Article number:
- 448
- Publication date:
- 2020-10-23
- Acceptance date:
- 2020-09-24
- DOI:
- EISSN:
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1757-6512
- Language:
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English
- Keywords:
- Pubs id:
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1140038
- Local pid:
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pubs:1140038
- Deposit date:
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2020-10-28
Terms of use
- Copyright holder:
- Meyer-Berg et al.
- Copyright date:
- 2020
- Rights statement:
- ©2020 The Author(s).
- Notes:
- Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
- Licence:
- CC Attribution (CC BY)
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