CRISPR Edits Genes to Treat Liver Disease in Mice

The gene-editing technology known as CRISPR/Cas9 has now been used to correct two different genetic liver diseases in mice — tyrosinemia Type I and ornithine transcarbamylase deficiency.

An earlier article reported the use of the CRISPR/Cas9 technique to successfully treat another genetic disorder — Duchenne muscular dystrophy — by cutting out a garbled section of DNA (CEP, Feb. 2016, pp. 6–9). The new research goes one step further by not only cutting out a mutated gene, but also pasting in a corrected sequence. To treat tyrosinemia Type I, researchers also incorporated a new nanoparticle-based step to reduce the chance of side effects.

“This is an approach that you could see being used in the clinic,” says Daniel Anderson, an associate professor of chemical engineering at the Massachusetts Institute of Technology.

Tyrosinemia Type I affects about one in every 100,000 infants worldwide, though it is particularly prevalent in some genetic subpopulations. In Quebec, for example, one in every 16,000 infants is affected. The disease is caused by a mutation in the FAH gene, which makes fumarylacetoacetate hydrolase, an enzyme that helps break down the protein tyrosine. Without this enzyme, tyrosine builds up in tissues and damages the liver, kidneys, and other organs. Without treatment, children typically die by age 10.

Anderson and his team had previously shown they could use CRISPR/Cas9 to treat tyrosinemia Type I by pumping large amounts of the...