Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/12176
Título
In vivo CRISPR/Cas9 targeting of fusion oncogenes for selective elimination of cancer cells.
Autor(es)
Martinez-Lage, M | Raul, Torres-Ruiz CNIO | Puig-Serra, P | Moreno-Gaona, P | Martin, M C | Moya, F J | Quintana-Bustamante, O | Garcia-Silva, S | Carcaboso, A M | Petazzi, P | Bueno, C | Mora, J | Peinado, H | Segovia, J C | Menendez, P | Rodriguez Perales, Sandra CNIO
Fecha de publicación
2020-10-11
Cita
Nat Commun. 2020;11(1):5060.
Idioma
Inglés
Tipo de documento
journal article
Resumen
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.
MESH
Animals | Base Sequence | CRISPR-Cas Systems | Cell Line, Tumor | Cell Proliferation | Doxorubicin | Fusion Proteins, bcr-abl | Gene Deletion | Genetic Loci | Genomic Instability | HEK293 Cells | Humans | Introns | Mice, Nude | Neoplasms | Oncogene Fusion | Oncogene Proteins, Fusion | RNA, Guide | Reproducibility of Results | Xenograft Model Antitumor Assays
Versión en línea
DOI
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