Hopes for human trials after mice cured by 'DNA editing'
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.
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.
Jennifer Doudna, of the University of California, Berkeley, who was one of the co-discoverers of the Crispr technique, said Professor Anderson's study was a "fantastic advance" because it demonstrated it was possible to cure adult animals living with a genetic disorder.
"Obviously, there would be numerous hurdles before such an approach could be used in people, but the simplicity of the approach, and the fact that it worked, really are very exciting," Professor Doudna said.
Delivering Crispr safely and efficiently to affected human cells is seen as one of the biggest obstacles to its widespread use in medicine.
Feng Zhang, of the Broad Institute at MIT, said that high-pressure injections are probably too dangerous to be used clinically, which is why he is working on ways of using Crispr to correct genetic faults in human patients with the help of adeno-associated viruses, which are known to be harmless.
But Professor Craig Mello of the University of Massachusetts Medical School said that delivering Crispr to the cells of the human brain and other vital organs would be difficult.
"Crispr therapies will no doubt be limited for the foreseeable future," he said. (© Independent News Service)
Independent News Service