A genetic disease has been cured in living, adult animals for the first time using a revolutionary genome-editing technique that can make the smallest changes to the vast database of the DNA molecule with pinpoint accuracy. Scientists have used the genome-editing technology to cure adult laboratory mice of an inherited liver disease by correcting a single “letter” of the genetic alphabet which had been mutated in a vital gene involved in liver metabolism. A similar mutation in the same gene causes the equivalent inherited liver disease in humans – and the successful repair of the genetic defect in laboratory mice raises hopes that the first clinical trials on patients could begin within a few years, scientists said. The success is the latest achievement in the field of genome editing. This has been transformed by the discovery of Crispr, a technology that allows scientists to make almost any DNA changes at precisely defined points on the chromosomes of animals or plants. Crispr – pronounced “crisper” – was initially discovered in 1987 as an immune defence used by bacteria against invading viruses.
Its powerful genome-editing potential in higher animals, including humans, was only fully realised in 2012 and 2013 when scientists showed that it can be combined with a DNA-sniping enzyme called Cas9 and used to edit the human genome. Since then there has been an explosion of interest in the technology because it is such a simple method of changing the individual letters of the human genome – the 3 billion “base pairs” of the DNA molecule – with an accuracy equivalent to correcting a single misspelt word in a 23-volume encyclopaedia. In the latest study, scientists at the Massachusetts Institute of Technology (MIT) used Crispr to locate and correct the single mutated DNA base pair in a liver gene known as LAH, which can lead to a fatal build-up of the amino acid tyrosine in humans and has to be treated with drugs and a special diet. The researchers effectively cured mice suffering from the disease by altering the genetic make-up of about a third of their liver cells using the Crispr technique, which was delivered by high-pressure intravenous injections. “We basically showed you could use the Crispr system in an animal to cure a genetic disease, and the one we picked was a disease in the liver which is very similar to one found in humans,” said Professor Daniel Anderson of MIT, who led the study. More