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dc.contributor.authorMeyer-Berg, Helena
dc.contributor.authorZhou Yang, Lucia
dc.contributor.authorde Lucas, Maria Pilar 
dc.contributor.authorZambrano, Alberto 
dc.contributor.authorHyde, Stephen C
dc.contributor.authorGill, Deborah R
dc.date.accessioned2021-02-01T18:13:37Z
dc.date.available2021-02-01T18:13:37Z
dc.date.issued2020
dc.identifier.citationStem Cell Res Ther. 2020 Oct 23;11(1):448.es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/11768
dc.description.abstractGene 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.es_ES
dc.description.sponsorshipThe material of this study was funded by the Wellcome Trust (110579/Z/15/Z) and the MRC studentship of HMB.es_ES
dc.language.isoenges_ES
dc.publisherBioMed Central (BMC) es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectAAV capsidses_ES
dc.subjectAAV serotypeses_ES
dc.subjectAlveolar type II cellses_ES
dc.subjectGene therapyes_ES
dc.subjectHuman embryonic stem cellses_ES
dc.subjectLung organoidses_ES
dc.subjectrAAVes_ES
dc.subjectStem cell-based tissue modeles_ES
dc.subjectViral infection modeles_ES
dc.subject.meshCell Line es_ES
dc.subject.meshDependovirus es_ES
dc.subject.meshGene Transfer Techniques es_ES
dc.subject.meshGenetic Therapy es_ES
dc.subject.meshGenetic Vectors es_ES
dc.subject.meshHuman Embryonic Stem Cells es_ES
dc.subject.meshHumans es_ES
dc.subject.meshLung es_ES
dc.subject.meshLung Diseases es_ES
dc.subject.meshModels, Biological es_ES
dc.subject.meshOrganoids es_ES
dc.subject.meshParenchymal Tissue es_ES
dc.titleIdentification of AAV serotypes for lung gene therapy in human embryonic stem cell-derived lung organoidses_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID33097094es_ES
dc.format.volume11es_ES
dc.format.number1es_ES
dc.format.page448es_ES
dc.identifier.doi10.1186/s13287-020-01950-xes_ES
dc.contributor.funderWellcome Trust 
dc.description.peerreviewedes_ES
dc.identifier.e-issn1757-6512es_ES
dc.relation.publisherversionhttps://doi.org/10.1186/s13287-020-01950-xes_ES
dc.identifier.journalStem cell research & therapyes_ES
dc.repisalud.centroISCIII::Unidad Funcional de Investigación de Enfermedades Crónicas (UFIEC)es_ES
dc.repisalud.institucionISCIIIes_ES
dc.rights.accessRightsopen accesses_ES


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Atribución 4.0 Internacional
Este Item está sujeto a una licencia Creative Commons: Atribución 4.0 Internacional