CRISPR/CAS9 approach targeting gene amplifications for efficient and selective elimination of cancer cells

M C Casado-Rosas(1) P Puig-Serra(1) M Martínez-Lage(1) A Nieto-Sánchez(1) A Alonso-Yañez(1) P Ojeda-Walczuk(1) S Rodriguez-Perales(1) R Torres-Ruiz(1,2) A Gonzalez-Murillo(3) M Ramirez-Orellana(3) P Río(2) A Valeria(4) M M Alonso(5) M García Moure(5) C Guerra(1) M García Moure(5) C Guerra(1) P Roda-Navarro(6) S Alegre(6)

1:Centro Nacional de Investigaciones Oncológicas; 2:CIEMAT; 3:Hospital Infantil Universitario Nno Jesus; 4:Hospital Universitario 12 de Octubre; 5:CIMA; 6:Universidad Complutense de Madrid, Facultad de Medicina

Cancer has classically been considered as a group of diseases triggered by a series of (epi-)genetic and chromosomal alterations. Among them, oncogene amplifications are common in many cancer types and are powerful drivers of several human cancers. Indeed, they are also related to poor outcomes due to drug resistance, thus there is a need for developing novel targeted therapies, with improved efficacy and fewer side-effects. We have developed a novel therapeutic approach using CRISPR/Cas9 for the selective targeting of NMYC oncogene amplification in the neuroblastoma rare cancer develops in nerve tissue of children under age 5. The promising experimental results obtained in immunosuppress in vivo models have led us to expand our strategy to other type of lethal cancers with no treatment characterized by the presence of oncogene amplifications. Our preliminary CRISPR-based approaches have successfully targets different types of cancer xenografts in in vivo studies.