First Step Toward CRISPR Cure of Lou Gehrig’s Disease


Source: University of California – Berkeley

Summary: Researchers for the first time have used CRISPR-Cas9 gene editing to disable a defective gene that causes amyotrophic lateral sclerosis (ALS) or Lou Gehrig’s disease, in mice, extending their lifespan by 25%.


Amyotrophic Lateral Sclerosis (ALS) or Lou Gehrig’s Disease is a progressive neurodegenerative disease characterized by loss of motor neurons in the spinal cord and brain. Particularly, autosomal dominant mutations in the SOD1 (Superoxide Dismutase 1) gene are responsible for about 20% of all inherited forms of the disease and about 2 % of all cases of ALS worldwide. The genetic cause is not known for ALS cases but all are accompanied by the premature death of motor neurons in the brain stem and spinal cord. The devastating disease usually strikes people between the ages of 40 and 70. Researchers from the University of California – Berkeley for the first time have used CRISPR-Cas9 gene editing to disable the defective gene that causes ALS in mice, extending their lifespan by 25%. The study findings were published in the journal Science Advances.

CRISPR-Cas9 gene editing to disable a defective gene that causes amyotrophic lateral sclerosis

The UC Berkeley team used an adeno-associated virus (AAV) to ferry genes for CRISPR-Cas9 into motor neurons to delay onset of symptoms of ALS in mice. Credit: David Schaffer graphic

The research team used a virus (adeno-associated virus) to seek out only motor neurons in the spinal cord and deliver a gene encoding the Cas9 protein into the nucleus. The Cas9 protein, molecular scissors that cut and disabled the mutant gene responsible for ALS. In this case, Cas9 was programmed to knock out the mutated gene SOD1. The onset or start of the disease was delayed by almost five weeks, and mice treated by the gene therapy lived about a month longer than the typical 4-month lifespan of mice with ALS. Healthy mice can live almost for 2 years. They are also working on a self-destruct switch for the Cas9 protein, so that once it knocks out the SOD1 gene, the Cas9 can be eliminated from the cell so as not to modify other genes accidentally or trigger an immune reaction.

Prof. David Schaffer said, “We have engineered new AAV vehicles that are capable of high-efficiency delivery to a number of cell and tissue targets in the body, and when CRISPR-Cas9 came along, we viewed it as a wonderful opportunity to put together this incredibly powerful cargo with the ability to carry that cargo to a number of cells and disease targets in vivo.”


More Information: Thomas Gaj et al, “In vivo genome editing improves motor function and extends survival in a mouse model of ALS,” Science Advances (2017). advances.sciencemag.org/content/3/12/eaar3952


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