Genetically Engineering the Nervous System with CRISPR-Cas

Abstract

The multitude of neuronal subtypes and extensive interconnectivity of the mammalian brain presents a substantial challenge to those seeking to decipher its functions. While the molecular mechanisms of several neuronal functions remain poorly characterized, advances in next-generation sequencing (NGS) and gene-editing technology have begun to close this gap. The clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein (CRISPR-Cas) system has emerged as a powerful genetic tool capable of manipulating the genome of essentially any organism and cell type. This technology has advanced our understanding of complex neurologic diseases by enabling the rapid generation of novel, disease-relevant in vitro and transgenic animal models. In this review, we discuss recent developments in the rapidly accelerating field of CRISPR-mediated genome engineering. We begin with an overview of the canonical function of the CRISPR platform, followed by a functional review of its many adaptations, with an emphasis on its applications for

POLR3-Related Leukodystrophy: Exploring Potential Therapeutic Approaches

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Genome Editing for CNS Disorders

“…Genome editing tools have been available for 30 years, but their limited efficacy, complex production and the lack of efficient delivery vehicles have delayed their clinical application. Over the last decade, more sophisticated and precise editing tools have rendered genome engineering not only promising for genebased therapeutic approaches, but also useful as a technique for basic biology, genetic diagnosis and drug discovery purposes (Doudna, 2020;Li et al, 2020;Sandoval et al, 2020;Wertz et al, 2020). Indeed, therapeutic genome editing is no longer a concept for the distant future, and several ex vivo and in vivo therapeutic approaches are currently undergoing clinical testing for the treatment of various diseases (Schacker and Seimetz, 2019;Li et al, 2020).…”

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