2026-07-21T14:13:59Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/117682025-05-27T10:50:05Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19617

00925njm 22002777a 4500 dc Meyer-Berg, Helena author Zhou Yang, Lucia author de Lucas, Maria Pilar author Zambrano, Alberto author Hyde, Stephen C author Gill, Deborah R author 2020 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. 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 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