Identification of AAV serotypes for lung gene therapy in human embryonic stem cell-derived lung organoids
<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 de...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
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BioMed Central
2020
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| _version_ | 1826302631006437376 |
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| author | Meyer-Berg, H Zhou Yang, L Pilar de Lucas, M Zambrano, A Hyde, SC Gill, DR |
| author_facet | Meyer-Berg, H Zhou Yang, L Pilar de Lucas, M Zambrano, A Hyde, SC Gill, DR |
| author_sort | Meyer-Berg, H |
| collection | OXFORD |
| description | <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> |
| first_indexed | 2024-03-07T05:50:31Z |
| format | Journal article |
| id | oxford-uuid:e8b58ee3-ac5e-48ed-b81e-d7562ff2de48 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:50:31Z |
| publishDate | 2020 |
| publisher | BioMed Central |
| record_format | dspace |
| spelling | oxford-uuid:e8b58ee3-ac5e-48ed-b81e-d7562ff2de482022-03-27T10:48:50ZIdentification of AAV serotypes for lung gene therapy in human embryonic stem cell-derived lung organoidsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e8b58ee3-ac5e-48ed-b81e-d7562ff2de48EnglishSymplectic ElementsBioMed Central2020Meyer-Berg, HZhou Yang, LPilar de Lucas, MZambrano, AHyde, SCGill, DR<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> |
| spellingShingle | Meyer-Berg, H Zhou Yang, L Pilar de Lucas, M Zambrano, A Hyde, SC Gill, DR Identification of AAV serotypes for lung gene therapy in human embryonic stem cell-derived lung organoids |
| title | Identification of AAV serotypes for lung gene therapy in human embryonic stem cell-derived lung organoids |
| title_full | Identification of AAV serotypes for lung gene therapy in human embryonic stem cell-derived lung organoids |
| title_fullStr | Identification of AAV serotypes for lung gene therapy in human embryonic stem cell-derived lung organoids |
| title_full_unstemmed | Identification of AAV serotypes for lung gene therapy in human embryonic stem cell-derived lung organoids |
| title_short | Identification of AAV serotypes for lung gene therapy in human embryonic stem cell-derived lung organoids |
| title_sort | identification of aav serotypes for lung gene therapy in human embryonic stem cell derived lung organoids |
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