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Real-time genome imaging of host interactions in adeno-associated virus genome release.

dc.rights.licenseopenen_US
dc.contributor.authorBUSTAMANTE-JARAMILLO, Luisa F
dc.contributor.authorYUE, Lei
dc.contributor.authorFINGAL, Joshua
dc.contributor.authorRYDELL, Gustaf
dc.contributor.authorJOHANSSON, Maria
dc.contributor.authorEDREIRA, Tomas
dc.contributor.authorMÜLLER, Oliver J
dc.contributor.authorHILLE, Susanne
dc.contributor.authorMÜLLER, Martin
dc.contributor.authorGALLARDO, Franck
dc.contributor.authorCHEN, Qingxin
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorBLONDOT, Marie-Lise
dc.contributor.authorKANN, Michael
dc.date.accessioned2025-07-08T08:26:29Z
dc.date.available2025-07-08T08:26:29Z
dc.date.issued2025-06-20
dc.identifier.issn2589-0042en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/207254
dc.description.abstractEnAdeno-associated virus (AAVs) with a self-complementary genome (sc) comprising a gene of interest are used in gene therapy. Their efficiency is limited but the molecular factors contributing to this restriction are poorly understood. We utilized scAAV2 containing a fluorescent protein-binding anchor sequence on its genome allowing visualization of released genomes by time-lapse microscopy. Pairing this technique with capsid staining, we showed that scAAV2 genome release was initiated by a partial genome exposure, triggered by elevated calcium levels while the capsids interacted with proteins of the nuclear pore. Genome release occurred subsequently requiring Rad52 decamerization in the vicinity of the host chromatin. A fraction of the released genomes was degraded by Mre11, an essential factor for chromatin stability, and cellular DNA double-strand breaks. These steps were key-factors limiting transduction, suggesting that temporary modulation of DNA damage-response-proteins is a promising way to increase scAAV efficiency in therapy.
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subject.enCellular therapy
dc.subject.enGenomics
dc.subject.enVirology
dc.subject.enGenomic analysis
dc.title.enReal-time genome imaging of host interactions in adeno-associated virus genome release.
dc.title.alternativeiScienceen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1016/j.isci.2025.112624en_US
dc.subject.halSciences du Vivant [q-bio]/Microbiologie et Parasitologieen_US
dc.identifier.pubmed40546945en_US
bordeaux.journaliScienceen_US
bordeaux.page112624en_US
bordeaux.volume28en_US
bordeaux.hal.laboratoriesMFP (Laboratoire Microbiologie Fondamentale et Pathogénicité) - UMR 5234en_US
bordeaux.issue6en_US
bordeaux.institutionCNRSen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcepubmed
hal.identifierhal-05149981
hal.version1
hal.date.transferred2025-07-08T08:26:36Z
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exporttrue
workflow.import.sourcepubmed
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=iScience&rft.date=2025-06-20&rft.volume=28&rft.issue=6&rft.spage=112624&rft.epage=112624&rft.eissn=2589-0042&rft.issn=2589-0042&rft.au=BUSTAMANTE-JARAMILLO,%20Luisa%20F&YUE,%20Lei&FINGAL,%20Joshua&RYDELL,%20Gustaf&JOHANSSON,%20Maria&rft.genre=article


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