Chapter 18 - CRISPR–Cas Gene Editing for Neurological Disease

Abstract

Clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated nuclease (Cas) gene editing technology, commonly referred to as CRISPR–Cas, is a revolutionary tool that is accelerating biomedical research. Modifying and regulating the genome with targeted precision and efficiency has never been easier in mammalian systems. Gene therapy with CRISPR–Cas is a potential therapeutic strategy for treating genetic neurological diseases, including Huntington disease, the spinocerebellar ataxias, fragile X syndrome, and amyotrophic lateral sclerosis. The tremendous progress with CRISPR–Cas in vitro—and, more recently, in vivo—holds great promise for future clinical translation. In this chapter, we describe CRISPR–Cas gene editing mechanisms and the engineering advances that are optimizing this technology. We then focus on its application and therapeutic potential in preclinical studies of models of neurological disease.