Impact of CRISPR in cancer drug discovery

Abstract

Precision gene editing enables massively parallel identification of cancer-promoting genes Since its discovery in 2012 as a gene-editing tool, CRISPR-Cas9 has been touted as a turning point for drug discovery. Indeed, CRISPR-based technologies have an unprecedented power to interrogate the mechanistic underpinnings of disease by systematically testing the cellular effects of targeted genetic alterations ( 1 ). Disease hallmarks specific to cancer, such as unchecked cell proliferation and drug resistance, readily lend themselves to massively parallel CRISPR screens. In these screens, individual cells harboring a guide RNA that also acts as a barcode for a DNA edit of interest may acquire a competitive or diminished proliferative advantage relative to other cells in the same test pool. This allows the perturbation of thousands of genes in a single experiment. The resulting genetic maps generated in cancer cell lines (CCLs) and in cancer-derived tissues now support exceptional speed and economy in the rationalization of new drug development and may shorten bench-to-bedside timelines.