Genome Editing with CRISPR‐Cas Systems

Since the advent of modern molecular biology, biologists have sought approaches to precisely manipulate DNA sequences to dissect the genetic underpinnings of cell biology and organismal physiology. Gene targeting—the first generation of genome editing—was born from the observation that exogenous DNA flanked by sequences that are homologous to endogenous genes could spontaneously integrate into chromosomal DNA at very low frequencies. CRISPR-Cas systems confer adaptive immunity to bacteria and archaea by mediating sequence-dependent recognition and destruction of invading genomes from bacteriophage or mobile genetic elements. A central challenge in modern genetics is understanding the contribution of single genetic variants to complex traits. Genome editing via gene disruption, gene insertion, or gene conversion holds therapeutic promise in a variety of disease contexts.