Gene editing advance in war on diseases

New ‘snipping’ technique could help with inherited illness such as sickle-cell anaemia and cystic fibrosis

Scientists have discovered a technique in gene editing which could help to cure a range of inherited diseases in the future. The new process could eventually allow doctors to fix the changes in genetic code responsible for many inherited diseases ranging from genetic blindness to cystic fibrosis.

SCIENTISTS have discovered a new technique in gene editing which could help to cure a range of inherited diseases in the future.

The new process could one day allow doctors to fix the single-letter changes in the genetic code responsible for many inherited diseases ranging from genetic blindness to sickle-cell anaemia, metabolic disorders and cystic fibrosis. The “base editor” is a molecular machine that directly converts one building block of DNA into another. DNA sequences contain four “base” chemicals that pair up on the molecule’s twin-stranded double helix in specific ways.

Together, guanine (G), adenine (A), thymine (T) and cytosine (C) make up the letters of the genetic code.

The new system converts the DNA base-pair A-T to G-C, a microscopically small effect that has major implications for science and medicine.

Roughly half the 32,000 single-letter changes in the genetic code known to be associated with human disease involve a change the other way, from G-C to A-T.

The technique employs a modified form of the “molecular scissors” geneediting tool CRISPR-CAS9, which has transformed genetics research since its power was first demonstrated in 2012. But unlike that original tool, it does not make changes by slicing through the double helix.

Professor David Liu, from Harvard University, who led the US research, said: “We developed a new base editor, a molecular machine, that in a programmable, irreversible, efficient and clean manner can correct these mutations in the genome of living cells.

“When targeted to certain sites in human genomic DNA, this conversion reverses the mutation that is associated with a particular disease.”

The “machine”, called an Adenine Base Editor (ABE), was tested in the laboratory by correcting the mutation responsible for hereditary haemochromatosis (HHC), a disease that causes iron overload in the body.

ABE was also used to install a beneficial mutation that protects against blood diseases including sickle cell anaemia.

Dr Liu said a lot more work needed to be done before the technique could be used to help human patients.

“We still have to deliver that machine, we have to test its safety, we have to assess its benefits in animals and patients and weigh them against side effects; we need to do many more things,” he said. British scientists called the research “exciting” and “incredibly powerful”.

Prof Robin Lovell-badge, group leader at The Francis Crick Institute, London, said: “This is both clever and important science. Many genetic diseases are due to alterations [mutations] where a single base pair has been substituted for another pair.

“This makes these new base editing methods of great value in both basic research to make disease models and, in theory, to correct genetic disease.

“Much more research will be needed to show the methods are entirely safe and, perhaps, to find ways to increase their efficiency, which is already at an impressive 50 per cent, but this is an exciting development.”

The results are reported in the journal Nature.

‘This is both important and clever science. This makes these new base editing methods of great value’