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dc.contributor.authorSharma, D.en
dc.contributor.authorAl-Khalidi, Rashaen
dc.contributor.authorEdgar, S.en
dc.contributor.authorAn, Q.en
dc.contributor.authorWang, Y.en
dc.contributor.authorYoung, Christopher N. J.en
dc.contributor.authorNowis, D.en
dc.contributor.authorGorecki, Dariuszen
dc.date.accessioned2017-12-20T10:49:36Z
dc.date.available2017-12-20T10:49:36Z
dc.date.issued2016-12
dc.identifier.citationSharma, D. et al. (2017). Co-delivery of indoleamine 2,3-dioxygenase prevents loss of expression of an antigenic transgene in dystrophic mouse muscles. Gene Therapy. 24(2), pp.113-119.en
dc.identifier.urihttp://hdl.handle.net/2086/15033
dc.description.abstractA significant problem affecting gene therapy approaches aiming at achieving long-term transgene expression is the immune response against the protein product of the therapeutic gene, which can reduce or eliminate the therapeutic effect. The problem is further exacerbated when therapy involves targeting an immunogenic tissue and/or one with a pre-existing inflammatory phenotype, such as dystrophic muscles. In this proof-of-principle study, we co-expressed a model antigen, bacterial β-galactosidase, with an immunosuppressive factor, indoleamine 2,3-dioxygenase 1 (IDO1), in muscles of the mdx mouse model of Duchenne muscular dystrophy. This treatment prevented loss of expression of the transgene concomitant with significantly elevated expression of T-regulatory (Treg) markers in the IDO1-expressing muscles. Moreover, co-expression of IDO1 resulted in reduced serum levels of anti-β-gal antibodies. These data indicate that co-expression of genes encoding immunomodulatory enzymes controlling kynurenine pathways provide a viable strategy for preventing loss of transgenes targeted into dystrophic muscles with pre-existing inflammation.en
dc.language.isoenen
dc.publisherSpringeren
dc.subjectIDOen
dc.subjectTDOen
dc.subjectT-regen
dc.subjectDMDen
dc.subjectmdxen
dc.subjectBeta-Galen
dc.subjectgene therapyen
dc.subjecttoleranceen
dc.titleCo-delivery of indoleamine 2,3-dioxygenase prevents loss of expression of an antigenic transgene in dystrophic mouse muscles.en
dc.typeArticleen
dc.identifier.doihttps://doi.org/10.1038/gt.2016.82
dc.peerreviewedYesen
dc.funderN/Aen
dc.projectidN/Aen
dc.cclicenceCC-BY-NCen
dc.date.acceptance2016-11-15en
dc.researchinstituteLeicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)en
dc.exception.ref2021codes254aen


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