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dc.contributor.authorMartinez-Lage, M
dc.contributor.authorRaul, Torres-Ruiz 
dc.contributor.authorPuig-Serra, P
dc.contributor.authorMoreno-Gaona, P
dc.contributor.authorMartin, M C
dc.contributor.authorMoya, F J
dc.contributor.authorQuintana-Bustamante, O
dc.contributor.authorGarcia-Silva, S
dc.contributor.authorCarcaboso, A M
dc.contributor.authorPetazzi, P
dc.contributor.authorBueno, C
dc.contributor.authorMora, J
dc.contributor.authorPeinado, H
dc.contributor.authorSegovia, J C
dc.contributor.authorMenendez, P
dc.contributor.authorRodriguez Perales, Sandra 
dc.date.accessioned2021-03-09T13:36:32Z
dc.date.available2021-03-09T13:36:32Z
dc.date.issued2020-10-11
dc.identifier.citationNat Commun. 2020;11(1):5060.es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/12176
dc.description.abstractFusion oncogenes (FOs) are common in many cancer types and are powerful drivers of tumor development. Because their expression is exclusive to cancer cells and their elimination induces cell apoptosis in FO-driven cancers, FOs are attractive therapeutic targets. However, specifically targeting the resulting chimeric products is challenging. Based on CRISPR/Cas9 technology, here we devise a simple, efficient and non-patient-specific gene-editing strategy through targeting of two introns of the genes involved in the rearrangement, allowing for robust disruption of the FO specifically in cancer cells. As a proof-of-concept of its potential, we demonstrate the efficacy of intron-based targeting of transcription factors or tyrosine kinase FOs in reducing tumor burden/mortality in in vivo models. The FO targeting approach presented here might open new horizons for the selective elimination of cancer cells.es_ES
dc.description.sponsorshipThis work was supported by grants from the Spanish National Research and Development Plan, Instituto de Salud Carlos III, and FEDER (PI17/02303 and DTS19/00111 to S.R-P.); AEI/MICIU EXPLORA Project BIO2017-91272-EXP and CaixaImpulse (CI18-00017;FuGe) to S.R-P. RT-R. is supported by a postdoctoral fellowship from the Asociacion Espanola Contra el Cancer (AECC). P.M. is supported by the European Research Council (CoG-2014-646903 and PoC-2018-811220), the Spanish Ministry of Science, Innovation and Universities (SAF2016), and the Catalunya Government (SGR330 and PERIS 2017). J.C.S. is supported by the Spanish Ministry of Science, Innovation and Universities (SAF2017-84248-P) and the Spanish Cell Therapy cooperative research network (TERCEL)(RD16/0011/0011). C.B. is supported by the AECC, Beca FERO, and the ISCIII/FEDER (PI17/01028). P.M. also acknowledges the financial support from the Obra Social La Caixa-Fundaci Josep Carreras. P.M. is an investigator of the Spanish Cell Therapy cooperative research network (TERCEL). A.M.C. acknowledges funding from ISCIII-FEDER (CP13/00189) and Xarxa de Bancs de Tumors de Catalunya (XBTC; sponsored by Pla Director d'Oncologia de Catalunya). We thank Dr Kenneth McCreath for critical reading of the paperes_ES
dc.language.isoenges_ES
dc.publisherNature Publishing Group es_ES
dc.type.hasVersionSMURes_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshAnimals es_ES
dc.subject.meshBase Sequence es_ES
dc.subject.meshCRISPR-Cas Systems es_ES
dc.subject.meshCell Line, Tumor es_ES
dc.subject.meshCell Proliferation es_ES
dc.subject.meshDoxorubicin es_ES
dc.subject.meshFusion Proteins, bcr-ables_ES
dc.subject.meshGene Deletion es_ES
dc.subject.meshGenetic Loci es_ES
dc.subject.meshGenomic Instability es_ES
dc.subject.meshHEK293 Cells es_ES
dc.subject.meshHumans es_ES
dc.subject.meshIntrons es_ES
dc.subject.meshMice, Nude es_ES
dc.subject.meshNeoplasms es_ES
dc.subject.meshOncogene Fusion es_ES
dc.subject.meshOncogene Proteins, Fusion es_ES
dc.subject.meshRNA, Guide es_ES
dc.subject.meshReproducibility of Results es_ES
dc.subject.meshXenograft Model Antitumor Assays es_ES
dc.titleIn vivo CRISPR/Cas9 targeting of fusion oncogenes for selective elimination of cancer cells.es_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.pubmedID33033246es_ES
dc.format.volume11es_ES
dc.format.number1es_ES
dc.format.page5060es_ES
dc.identifier.doi10.1038/s41467-020-18875-xes_ES
dc.contributor.funderInstituto de Salud Carlos III 
dc.contributor.funderUnión Europea. Comisión Europea 
dc.contributor.funderAsociación Española Contra el Cáncer 
dc.contributor.funderGovernment of Catalonia (España) 
dc.contributor.funderRETICS-Terapia Celular (TERCEL-ISCIII) (España) 
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) 
dc.contributor.funderFundación La Caixa 
dc.description.peerreviewedNoes_ES
dc.identifier.e-issn2041-1723es_ES
dc.relation.publisherversionhttps://doi.org/10.1038/s41467-020-18875-xes_ES
dc.identifier.journalNature communicationses_ES
dc.repisalud.institucionISCIIIes_ES
dc.repisalud.orgCNIOCNIO::Unidades técnicas::Unidad de Citogenética Moleculares_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI17/02303es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/DTS19/00111es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI17/01028es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/CP13/00189es_ES
dc.rights.accessRightsopen accesses_ES


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