Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/261299
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | CRISPR-Cas9 Technology as a Tool to Target Gene Drivers in Cancer: Proof of Concept and New Opportunities to Treat Chronic Myeloid Leukemia |
Autor: | Vuelta, Elena; Ordóñez, José Luis CSIC ORCID CVN; Alonso-Pérez, Verónica CSIC ORCID; Méndez Sánchez, Lucía; Hernández-Carabias, Patricia; Saldaña, Raquel; Sevilla, Julián; Sebastián, Elena; Muntión, Sandra; Sánchez-Guijo, Fermín M. CSIC ORCID; Hernández, Jesús M. CSIC ORCID ; García-Tuñón, Ignacio CSIC ORCID CVN; Sánchez-Martín, M. | Fecha de publicación: | ago-2021 | Editor: | Mary Ann Liebert | Citación: | The CRISPR Journal 4(4): 519-535 (2021) | Resumen: | Chronic myeloid leukemia (CML) is a hematopoietic malignancy produced by a unique oncogenic event involving the constitutively active tyrosine-kinase (TK) BCR/ABL1. TK inhibitors (TKI) changed its prognosis and natural history. Unfortunately, ABL1 remains unaffected by TKIs. Leukemic stem cells (LSCs) remain, and resistant mutations arise during treatment. To address this problem, we have designed a therapeutic CRISPR-Cas9 deletion system targeting BCR/ABL1. The system was efficiently electroporated to cell lines, LSCs from a CML murine model, and LSCs from CML patients at diagnosis, generating a specific ABL1 null mutation at high efficiency and allowing the edited leukemic cells to be detected and tracked. The CRISPR-Cas9 deletion system triggered cell proliferation arrest and apoptosis in murine and human CML cell lines. Patient and murine-derived xenografts with CRISPR-edited LSCs in NOD SCID gamma niches revealed that normal multipotency and repopulation ability of CRISPR edited LSCs were fully restored. Normal hematopoiesis was restored, avoiding myeloid bias. To the best of our knowledge, we show for the first time how a CRISPR-Cas9 deletion system efficiently interrupts BCR/ABL1 oncogene in primary LSCs to bestow a therapeutic benefit. This study is a proof of concept for genome editing in all those diseases, like CML, sustained by a single oncogenic event, opening up new therapeutic opportunities. | Versión del editor: | http://dx.doi.org/10.1089/crispr.2021.0009 | URI: | http://hdl.handle.net/10261/261299 | DOI: | 10.1089/crispr.2021.0009 | ISSN: | 2573-1599 | E-ISSN: | 2573-1602 |
Aparece en las colecciones: | (IBMCC) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
accesoRestringido.pdf | 15,38 kB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
SCOPUSTM
Citations
2
checked on 29-abr-2024
WEB OF SCIENCETM
Citations
2
checked on 29-feb-2024
Page view(s)
69
checked on 30-abr-2024
Download(s)
22
checked on 30-abr-2024
Google ScholarTM
Check
Altmetric
Altmetric
NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.