Anaemia

CRISPR-gene editing may enable treatment for hemoglobinopathies 


In a landmark study that could lead to new therapies for sickle cell anaemia and other blood disorders, Sydney-led researchers have used CRISPR-gene editing to introduce beneficial natural mutations into blood cells to boost their production of foetal haemoglobin.

The research solves a 50-year-old mystery about how these mutations – which are naturally carried by a small percentage of people – operate and alter the expression of human genes.

The study, by an international team led by University of NSW Professor Merlin Crossley, a molecular biologist, is published in the journal Nature Genetics.

“Our new approach can be seen as a forerunner to ‘organic gene therapy’ for a range of common inherited blood disorders including beta thalassaemia and sickle cell anaemia,” says Professor Crossley, who is also UNSW Deputy Vice-Chancellor Academic.

“It is organic because no new DNA is introduced into the cells; rather we engineer in naturally occurring, benign mutations that are known to be beneficial to people with these conditions.

“It should prove to be a safe and effective therapy, although more research would be needed to scale the processes up into effective treatments.”

Professor Crossley says the foetal haemoglobin gene is naturally silenced after birth. And for 50 years, researchers have been competing furiously to find out how it is switched off, so it can be turned back on.

“Our study, which is the culmination of many years of work, solves that mystery.

“We have found that two genes, called BCL11A and ZBTB7A, switch off the foetal haemoglobin gene by binding directly to it. And the beneficial mutations work by disrupting the two sites where these two genes bind.”

“This landmark finding not only contributes to our appreciation of how these globin genes are regulated. It means we can now shift our focus to developing therapies for these genetic diseases using CRISPR to target precise changes in the genome,” says Professor Crossley.

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