2026-06-14T03:38:32Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/121762024-11-29T17:05:04Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Martinez-Lage, M
author
Raul, Torres-Ruiz
author
Puig-Serra, P
author
Moreno-Gaona, P
author
Martin, M C
author
Moya, F J
author
Quintana-Bustamante, O
author
Garcia-Silva, S
author
Carcaboso, A M
author
Petazzi, P
author
Bueno, C
author
Mora, J
author
Peinado, H
author
Segovia, J C
author
Menendez, P
author
Rodriguez Perales, Sandra
funder
Instituto de Salud Carlos III
funder
Unión Europea. Comisión Europea
funder
Asociación Española Contra el Cáncer
funder
Government of Catalonia (España)
funder
RETICS-Terapia Celular (TERCEL-ISCIII) (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Fundación La Caixa
2021-03-09T13:36:32Z
2021-03-09T13:36:32Z
2020-10-11
Nat Commun. 2020;11(1):5060.
10.1038/s41467-020-18875-x
2041-1723
Nature communications
33033246
http://hdl.handle.net/20.500.12105/12176
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.
eng
In vivo CRISPR/Cas9 targeting of fusion oncogenes for selective elimination of cancer cells.
journal article
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
URL
https://repisalud.isciii.es/bitstreams/e66673f4-0545-4926-b647-3c4775e291ff/download
File
MD5
f9c5d02bc8beb75ecb15afb4776b5ea1
1914089
application/pdf
InvivoCRISPRCas9targeting_2020.pdf
URL
https://repisalud.isciii.es/bitstreams/6b6fa10d-6c1f-42ca-83db-8f38777fe257/download
File
MD5
3e869b2bf9a06596a36829cda5816408
14334053
application/pdf
41467_2020_18875_MOESM1_ESM.pdf
URL
https://repisalud.isciii.es/bitstreams/9ac146bd-70af-4c5f-a722-3c2cda1ec550/download
File
MD5
7b055442a170e0d57c7c5847614f32f8
151977
application/pdf
41467_2020_18875_MOESM2_ESM.pdf
URL
https://repisalud.isciii.es/bitstreams/1359e024-eb6c-4e6a-b930-edde0050806f/download
File
MD5
fdb1c184a8c317f9c24eb494bb47ee58
90543
application/pdf
41467_2020_18875_MOESM3_ESM.pdf
URL
https://repisalud.isciii.es/bitstreams/49e409c4-3ec5-48d6-a513-c6ebae5c9847/download
File
MD5
ba9c25b6f0e4df126b489203c3af9a61
84470
text/plain
InvivoCRISPRCas9targeting_2020.pdf.txt
URL
https://repisalud.isciii.es/bitstreams/3358ae55-335b-4133-b543-cfd72137ecb6/download
File
MD5
fe3ecee9aa0d2153613233e624b6427b
17770
text/plain
41467_2020_18875_MOESM1_ESM.pdf.txt
URL
https://repisalud.isciii.es/bitstreams/798006a8-5bd0-4f54-a434-fcec2b36e60a/download
File
MD5
25884bf5c23aa49dd7df7d642d98d2e5
20660
text/plain
41467_2020_18875_MOESM2_ESM.pdf.txt
URL
https://repisalud.isciii.es/bitstreams/dd645194-e0cf-4604-8aeb-8d6a15dfcb12/download
File
MD5
54cfd914baf2afa2edcb1576828fc940
11846
text/plain
41467_2020_18875_MOESM3_ESM.pdf.txt