CRISPR-Based Gene Editing Techniques in Pediatric Neurological Disorders.

ABSTRACT

The emergence of gene editing technologies offers a unique opportunity to develop mutation-specific treatments for pediatric neurological disorders. Gene editing systems can potentially alter disease trajectory by correcting dysfunctional mutations or therapeutically altering gene expression. Clustered regularly interspaced short palindromic repeats (CRISPR)-based approaches are attractive gene therapy platforms to personalize treatments because of their specificity, ease of design, versatility, and cost. However, many such approaches remain in the early stages of development, with ongoing efforts to optimize editing efficiency, minimize unintended off-target effects, and mitigate pathologic immune responses. Given the rapid evolution of CRISPR-based therapies, it is prudent for the clinically based child neurologist to have a conceptual understanding of what such therapies may entail, including both benefits and risks and how such therapies may be clinically applied. In this review, we describe the fundamentals of CRISPR-based therapies, discuss the opportunities and challenges that have arisen, and highlight preclinical work in several pediatric neurological diseases.