The potential of gene editing for Huntington’s disease

Abstract

Huntington’s disease (HD) is a dominantly inherited neurodegenerative disorder caused by a trinucleotide repeat expansion in the huntingtin gene resulting in long stretches of polyglutamine repeats in the huntingtin protein. The disease involves progressive degeneration of neurons in the striatum and cerebral cortex resulting in loss of control of motor function, psychiatric problems, and cognitive deficits. There are as yet no treatments that can slow disease progression in HD. Recent advances in gene editing using clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated protein 9 (Cas9) systems and demonstrations of their ability to correct gene mutations in animal models of a range of diseases suggest that gene editing may prove effective in preventing or ameliorating HD. Here we describe (i) potential CRISPR-Cas designs and cellular delivery methods for the correction of mutant genes that cause inherited diseases, and (ii) recent preclinical findings demonstrating the efficacy of such gene-editing approaches in animal models, with a focus on HD.