TORONTO - Clustered, regularly interspaced, short palindromic repeat associated (CRISPR-Cas) systems are acquired systems of immunity widespread in archaea and bacteria. RNA-guided nucleases from CRISPR-Cas systems are regarded as the most reliable tools for genome editing and engineering today. Their first manifestation came in 1987 when an unusual repetitive DNA sequence - afterwards defined as a CRISPR - was found in the Escherichia coli genome during an analysis of genes involved in phosphate metabolism.²

Similar sequence patterns were also reported in a range of other bacteria in halophilic archaea, suggesting a key role for such evolutionarily conserved clusters of repeated sequences. 

A critical step toward the functional characterization of CRISPR-Cas systems was the recognition of a link between CRISPRs and the associated Cas proteins initially hypothesized to be involved in DNA repair in hyperthermophilic archaea. Comparative genomics, structural biology, and advanced biochemistry were then able to work hand-in-hand - not only culminating in the explosion of genome editing tools based on CRISPR-Cas9 and other class II CRISPR-Cas systems, but also providing insights into the origin and evolution of this system from mobile genetic element-denoted casposons.

This article describes how CRISPR was first identified, key discoveries leading to its development as a gene-editing tool, its astounding uses, and how it continues to develop beyond gene editing.²

Introduction
The CRISPR-Cas system first evolved in microbes as a defense against invasive phages. Today, it forms the basis for the most exciting and fastest developing set of tools in biotechnology, which enable editing of any gene in any cellular organism or tissue. CRISPR-Cas promises unprecedented advances in fields from health