Enhanced CRAd activity using enhancer motifs driven by a nucleosome positioning sequence

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dc.contributor.authorBravo, S.
dc.contributor.authorNúñez, F.
dc.contributor.authorCruzat, F.
dc.contributor.authorCafferata, E.
dc.contributor.authorDe Ferrari, G.
dc.contributor.authorMontecino, M.
dc.contributor.authorPodhajcer, O.
dc.date.accessioned2023-05-26T16:31:21Z
dc.date.available2023-05-26T16:31:21Z
dc.date.issued2013
dc.descriptionIndexación: Scopus.es
dc.description.abstractCancer development involves changes driven by the epigenetic machinery, including nucleosome positioning. Recently, the concept that adenoviral replication may be driven by tumor specific promoters (TSPs) gained support, and several conditionally replicative adenoviruses (CRAd) exhibited therapeutic efficacy in clinical trials. Here, we show for the first time that placing a nucleosome positioning sequence (NPS) upstream of a TSP combined with Wnt-responsive motifs (pART enhancer) enhanced the TSP transcriptional activity and increased the lytic activity of a CRAd. pART enhanced the transcriptional activity of the gastrointestinal cancer (GIC)-specific REG1A promoter (REG1A-pr); moreover, pART also increased the in vitro lytic activity of a CRAd whose replication was driven by REG1A-Pr. The pART enhancer effect in vitro and in vivo was strictly dependent on the presence of the NPS. Indeed, deletion of the NPS was strongly deleterious for the in vivo antitumor efficacy of the CRAd on orthotopically established pancreatic xenografts. pART also enhanced the specific activity of other heterologous promoters; moreover, the NPS was also able to enhance the responsiveness of hypoxia- and NFκB-response elements. We conclude that NPS could be useful for gene therapy approaches in cancer as well as other diseases.es
dc.description.urihttps://www-sciencedirect-com.recursosbiblioteca.unab.cl/science/article/pii/S1525001616319645?via%3Dihub
dc.identifier.citationMolecular Therapy, Volume 21, Issue 7, Pages 1403 - 141, 2July 2013es
dc.identifier.doi10.1038/mt.2013.93
dc.identifier.issn1525-0016
dc.identifier.urihttps://repositorio.unab.cl/xmlui/handle/ria/50047
dc.language.isoenes
dc.publisherCell Presses
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
dc.subjectAdenoviridaees
dc.subjectAdenovirus Receptores
dc.subjectHuman Adenoviruseses
dc.subjectconditionally replicating adenoviruses
dc.subjectimmunoglobulin enhancer binding proteines
dc.subjectmessenger RNAes
dc.titleEnhanced CRAd activity using enhancer motifs driven by a nucleosome positioning sequencees
dc.typeArtículoes
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