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| Home > Articles > Published articles > In vivo CRISPR/Cas9 targeting of fusion oncogenes for selective elimination of cancer cells |
(Centro Nacional de Investigaciones Oncológicas) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Centro Nacional de Investigaciones Oncológicas) (Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz) (Centro Nacional de Investigaciones Oncológicas) (Hospital Sant Joan de Déu (Barcelona, Catalunya)) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Centro Nacional de Investigaciones Oncológicas) (Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Centro Nacional de Investigaciones Oncológicas)| Date: | 2020 |
| Abstract: | Fusion 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. |
| Grants: | Agència de Gestió d'Ajuts Universitaris i de Recerca SAF2017-84248-P Agència de Gestió d'Ajuts Universitaris i de Recerca SGR330 Instituto de Salud Carlos III CP13-00189 Instituto de Salud Carlos III PI17-01028 Instituto de Salud Carlos III DTS19-00111 Ministerio de Ciencia e Innovación BIO2017-91272-EXP Ministerio de Ciencia e Innovación SAF2016 |
| Note: | This work was supported by CaixaImpulse (CI18-00017;FuGe) to S.R-P. RT-R. is supported by a postdoctoral fellowship from the Asociación Española Contra el Cáncer (AECC). J.C.S. is supported by the Spanish Cell Therapy cooperative research network (TERCEL)(RD16/0011/0011). P.M. also acknowledges the financial support from the Obra Social La Caixa-Fundaciò Josep Carreras. P.M. is an investigator of the Spanish Cell Therapy cooperative research network (TERCEL). A.M.C. acknowledges funding fromXarxa de Bancs de Tumors de Catalunya (XBTC; sponsored by Pla Director d'Oncologia de Catalunya). |
| Note: | Altres ajuts: PERIS/2017 |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Gene therapy ; Cancer |
| Published in: | Nature communications, Vol. 11 Núm. 1 (january 2020) , p. 5060, ISSN 2041-1723 |
