2026-07-21T14:14:09Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/117682025-05-27T10:50:05Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19617
Repisalud
author
Meyer-Berg, Helena
author
Zhou Yang, Lucia
author
de Lucas, Maria Pilar
author
Zambrano, Alberto
author
Hyde, Stephen C
author
Gill, Deborah R
funder
Wellcome Trust
2021-02-01T18:13:37Z
2021-02-01T18:13:37Z
2020
Stem Cell Res Ther. 2020 Oct 23;11(1):448.
10.1186/s13287-020-01950-x
1757-6512
Stem cell research & therapy
33097094
http://hdl.handle.net/20.500.12105/11768
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.
eng
AAV capsids
AAV serotypes
Alveolar type II cells
Gene therapy
Human embryonic stem cells
Lung organoids
rAAV
Stem cell-based tissue model
Viral infection model
Identification of AAV serotypes for lung gene therapy in human embryonic stem cell-derived lung organoids
research article
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IdentificationOfAAVSerotypes_2020.pdf
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IdentificationOfAAVSerotypes_2020.pdf.txt