CRISPR‐Cas9 : A New Tool for Gene Therapy

Abstract

Programmable RNA (ribonucleic acid)‐guided genome engineering using the recently developed clustered regularly interspaced short palindromic repeats (CRISPR)‐associated (CRISPR Cas) system has revolutionised the field of gene editing owing its adaptability and versatility in addressing a wide range of biological questions. It relies on harnessing critical components of the bacterial acquired immune system, namely the Cas9 protein and its associated guide ribonucleic acid (gRNA), to selectively target and edit a desired gene, thereby underscoring its potential as a promising gene therapy agent. Its application, however, encompasses several critical parameters, ranging from safe delivery of the agent to tackling issues of unintended off‐targeting in the genome. Similar to its predecessor molecular scissors, namely zinc finger nucleases (ZFNs) and transcription activator‐like nucleases (TALENs), CRISPR‐Cas9 has been studied extensively along these lines to facilitate its use in therapeutic interventions and has shown some early promise in taking benchtop discoveries to the clinic. Key Concepts CRISPR‐Cas9 is the most recent addition to the repertoire of ‘molecular scissors’ for genome editing. The system relies on an RNA‐guided protein that can make desirable changes in the genome. CRISPR‐Cas9 has shown a lot of promise for in vivo and in vitro editing, which can be translatable for disorders, particularly monogenic ones. Components of the system have been used for correcting several disease‐relevant mutations in mice through zygotic, somatic or ex vivo gene‐editing strategies. The success of CRISPR as a therapeutic tool depends on its inherent properties of efficiency and specificity. Protein and sgRNA engineering combined with improved delivery strategies have led to the discovery of potent CRISPR‐based therapy products. The first clinical trials using CRISPR are currently under process.