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dc.contributor.authorGuilbaud, Mickaël
dc.contributor.authorDevaux, Marie
dc.contributor.authorCouzinié, Celia
dc.contributor.authorLe Duff, Johanne
dc.contributor.authorToromanoff, Alice
dc.contributor.authorVandamme, Céline
dc.contributor.authorJaulin, Nicolas
dc.contributor.authorGernoux, Gwladys
dc.contributor.authorLarcher, Thibaut
dc.contributor.authorMoullier, Philippe
dc.contributor.authorLe Guiner, Caroline
dc.contributor.authorAdjali, Oumeya
dc.date.accessioned2019-04-24T11:25:19Z
dc.date.available2019-04-24T11:25:19Z
dc.date.issued2019
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/7563
dc.description.abstractAnti-transgene immune responses elicited after intramuscular (i.m.) delivery of recombinant adeno-associated virus (rAAV) have been shown to hamper long-term transgene expression in large-animal models of rAAV-mediated gene transfer. To overcome this hurdle, an alternative mode of delivery of rAAV vectors in nonhuman primate muscles has been described: the locoregional (LR) intravenous route of administration. Using this injection mode, persistent inducible transgene expression for at least 1 year under the control of the tetracycline-inducible Tet-On system was previously reported in cynomolgus monkeys, with no immunity against the rtTA transgene product. The present study shows the long-term follow-up of these animals. It is reported that LR delivery of a rAAV2/1 vector allows long-term inducible expression up to at least 5 years post gene transfer, with no any detectable host immune response against the transactivator rtTA, despite its immunogenicity following i.m. gene transfer. This study shows for the first time a long-term regulation of muscle gene expression using a Tet-On-inducible system in a large-animal model. Moreover, these findings further confirm that the rAAV LR delivery route is efficient and immunologically safe, allowing long-term skeletal muscle gene transfer.
dc.language.isoenglanti
dc.publisherMary Ann Liebert Inc
dc.relation.ispartofseriesHuman gene therapy
dc.relation.urihttp://dx.doi.org/10.1089/hum.2018.234
dc.rightsAll rights reserved
dc.subjectAAV
dc.subjectgene transfer
dc.subjectlocoregional delivery
dc.subjectnon-human primate
dc.subjectimmunogenicty
dc.subjectlong-term follow-up
dc.title5 years of successful inducible transgene expression following locoregional AAV delivery in nonhuman primates with no detectable immunity
dc.description.versionfinal draft
dc.contributor.departmentSchool of Medicine / Clinical Medicine
uef.solecris.id60850785en
dc.type.publicationTieteelliset aikakauslehtiartikkelit
dc.rights.accessrights© Mary Ann Liebert, Inc
dc.relation.doi10.1089/hum.2018.234
dc.description.reviewstatuspeerReviewed
dc.format.pagerange802-813
dc.relation.issn1043-0342
dc.relation.issue7
dc.relation.volume30
dc.rights.accesslevelopenAccess
dc.type.okmA1
uef.solecris.openaccessEi


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