New Targets in Treating Amyotrophic Lateral Sclerosis (ALS), a Neurodegenerative Disease, Identified Using CRISPR

Amyotrophic Lateral Sclerosis (ALS) is a group of rare progressive neurological diseases that causes the death of neurons controlling voluntary muscle movements. Abnormal protein accumulation is one of the major characteristics of ALS and believed to be the cause of neuron toxicity. However, our understanding of ALS development is very limited and no effective treatment is available for patients yet.

Recently, by using genome-wide CRISPR single-guide RNA (sgRNA) libraries, scientists from Stanford University School of Medicine performed comprehensive and systematic genome-wide knockout screens in human cell lines and targeted mouse primary neuron screens and identified genetic modifiers of the toxicity of the ALS proteins. They identified about 200 genes that can either protect the cells from or sensitize them to the toxic proteins. Further knockout screens in mouse neurons showed that some of these genes are potent protectors of the ALS proteins and might be potential drug targets for ALS treatment. Applying genome-wide CRISPR screens in research is an new exciting approach for understanding disease causes that we were not able to find before.

• Nicholas J. Kramer, et al.CRISPR–Cas9 screens in human cells and primary neurons identify modifiers of C9ORF72 dipeptide-repeat-protein toxicity.  Nature Genetics, 2018; DOI: 10.1038/s41588-018-0070-7.

Genome-wide and pathway specific gRNA libraries for efficient screening