The prospects of CRISPR-based genome engineering in the treatment of neurodegenerative disorders

Over the past few decades, as gene discovery methods and sequencing technologies have evolved, many genetic variations that significantly increase the risk of or cause neurodegenerative diseases have been identified. However, knowledge of those pathogenic mutations and subsequent mechanism-focused studies has rarely yielded effective treatments, warranting alternative strategies for refining rational therapeutic targets. Nevertheless, with the evolution of gene targeting methods, it has been increasingly recognized that the disease-causing gene itself is the best therapeutic target even when we do not have a full understanding of its biological functions. Considering this, CRISPR/Cas gene editing technology offers the promise of permanently silencing or correcting the disease-causing mutations, potentially overcoming key limitations of RNA-targeting approaches. The versatile CRISPR/Cas-based strategies have the potential to become treatment options for challenging disorders such as neurodegenerative diseases. Here, we summarize recent reports of preclinical applications of CRISPR/Cas in models of neurodegenerative disorders to provide perspectives on therapeutic gene editing for diseases of the nervous system.