Parents of newborns may be familiar with the metabolic disorder phenylketonuria: in Switzerland, all newborn babies are screened for this genetic disease. If a baby is found to have phenylketonuria, he or she requires a special diet so that the amino acid phenylalanine does not accumulate in the body. Excess phenylalanine delays mental and motor development. If left untreated, the children may suffer massive mental disability. The cause of this metabolic disorder is a mutation in a gene that provides the blueprint for the enzyme phenylalanine hydroxylase (Pah). This enzyme, which is produced by the cells of the liver, metabolizes phenylalanine. The disorder is referred to as "autosomal recessive"--the child develops the disease if he or she inherits one mutated Pah gene from the mother and one from the father. There has been no cure for this disorder to date. A team of researchers led by ETH Zurich professor Gerald Schwank has now taken advantage of a method to correct both mutated genes in the liver cells and thus heal the disease. (Editor’s Note: ETH Zurich is a science, technology, engineering, and mathematics university in the city of Zürich, Switzerland.) Dr. Schwank’s team has succeeded, at least in mice. With the help of a CRISPR/Cas9 system extended by one enzyme, the researchers changed the sequence of the DNA building blocks for the Pah corresponding gene in adult mice. The mouse liver cells were subsequently able to produce functioning Pah enzymes, and the mice were healed. The work was reported online on October 8, 2018 in Nature Medicine. The article is titled “Treatment of a Metabolic Liver Disease by In Vivo Genome Base Editing in Adult Mice.” Following are more details on the work.
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