Way to switch on a gene in red blood cells discovered

Scientists from University of New South Wales (UNSW) in Australia have discovered a way to change a single base of DNA in human red blood cells (RBCs), triggering them to produce more oxygen-carrying haemoglobin.

Hemoglobin is the protein molecule in red blood cells that carries oxygen from the lungs to the body’s tissues and returns carbon dioxide from the tissues back to the lungs. Throughout our lives we produce two different kinds: foetal haemoglobin – which is able to quickly suck up oxygen from our mothers’ blood – and adult haemoglobin.

Mutations in adult haemoglobin are extremely common. Carrying just one of the mutations isn’t so bad, but if someone inherits mutant haemoglobin genes from both parents, it can severely damage haemoglobin production and cause life-threatening conditions, such as sickle cell anaemia and thalassaemia.

However, a small group of these people also inherit a third mutation in their foetal haemoglobin, which results in it being produced after birth, and as a result, their symptoms are greatly reduced. “This good mutation keeps their foetal haemoglobin gene switched on for the whole of their lives, and reduces their symptoms significantly,” said Crossley.

“An exciting new age of genome editing is beginning, now that single genes within our vast genome can be precisely cut and repaired,” study leader and Dean of Science at UNSW, Merlin Crossley, said in a press statement. “Our laboratory study provides a proof of concept that changing just one letter of DNA in a gene could alleviate the symptoms of sickle cell anaemia and thalassaemia – inherited diseases in which people have damaged haemoglobin.”

The group exploited the effect of the mutation that occurs in foetal haemoglobin. To try to recreate this beneficial mutation, the team used genome-editing proteins known as TALENs, which cut a gene at a specific point and then drop off the desired piece of DNA to be inserted. The cell then naturally tries to heal the DNA by patching it up with spare DNA lying around.

This world-first technique could lead to new treatments for sickle cell anaemia and other life-threatening blood disorders. This technique activates a naturally occurring gene that’s normally dormant after birth.

“However, more research is needed before it can be tested in people as a possible cure for serious blood diseases,” Crossley said.

The results were published in Nature Communications.