CRISPR/Cas9-based Genome and Epigenome Editing in Neuroscience Research

Abstract

In less than a decade, the CRISPR/Cas9-based revolution of genome and epigenome editing has made a remarkable impact on neuroscience. A variety of genome and epigenome editing tools have been applied to address questions pertinent to the development, function and pathologies of the nervous system. This chapter discusses the major technological advances of the CRISPR/Cas9 system that enable genome and epigenome editing, transcriptional control, visualization of genomic loci, base editing and prime editing in the brain. Since spatial and temporal specificity of gene targeting are of paramount importance for neuroscience, this chapter discusses various methodologies that enable such targeting in an inducible manner. Specifically addressed are various ways of acutely delivering CRISPR/Cas9 components to either an embryonic or an adult animal brain, including methods such as virus injection, in utero electroporation, injection of nanocomplexes, and others. This chapter further discusses the possibilities of genome and epigenome editing across various model systems relevant for neuroscience, ranging from genetically modified rodents, carnivores, non-human primates and other animals to IPSC-derived neurons and cerebral organoids. Finally, the current achievements and future challenges in applying CRISPR/Cas9-mediated genome and epigenome editing to study, prevent and cure various neurological and psychiatric diseases are discussed.