Gene editing technology could pave way for sickle cell anemia cure

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Blood disorders are generally life threatening unless patients are constantly provided life-long treatments including blood transfusions and medication, which take a toll not only on their overall quality of life, but also set them back financially. However, genome editing is proving to be a promising method that tackles disorders at the genetic level to alleviate the condition and make patients disease free.

One such development has recently been published in the journal Nature Communications, wherein researchers at University of New South Wales managed to change just a single letter of the DNA of human red blood cells in the laboratory to increase the cells’ production of oxygen-carrying haemoglobin. Researchers peg this as a promising development, which could eventually pave way for a cure for sickle cell anaemia and other blood disorders.

The technique developed by UNSW researchers makes use of a beneficial, naturally-occurring genetic mutation by introducing it into cells, which switches on a sleeping gene that is active in the womb but turned off in most people after birth. Researchers say that the genetic variation that they introduced is already present in nature because of which they believe that their approach should be effective and safe. However, they caution that much more research is needed before it can tested in people.

“An exciting new age of genome editing is beginning, now that single genes within our vast genome can be precisely cut and repaired,” says study leader, Dean of Science at UNSW, Professor Merlin Crossley. “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 study was conducted by Professor Crossley, UNSW PhD student Beeke Wienert, and colleagues.

Haemoglobin – the oxygen transporting molecule

Researchers say that we humans produce two different kinds of haemoglobin – one kind is produced during development of foetus in the womb dubbed the foetal haemoglobin, which is regulated by a gene that is switched on at that time only. This foetal haemoglobin has a high affinity for oxygen allowing the baby to snatch oxygen from its mother’s blood says Professor Crossley. After we are born, this foetal haemoglobin gene is shut off and the adult haemoglobin gene is switched on.

Researchers say that mutations affecting adult haemoglobin are one of the most common of all human genetic mutations with an estimated five per cent of the world’s population carrying a defective adult haemoglobin gene.

When people inherit two mutant genes – one from their mother and one from their father – they end up having damaged haemoglobin because of which they suffer from life-threatening diseases such as sickle cell anaemia and thalassaemia.

Researchers say that a small proportion of people with damaged adult haemoglobin have an additional, beneficial mutation in the foetal haemoglobin gene and this good mutation keeps their foetal haemoglobin gene switched on for the whole of their lives and reduces their symptoms significantly.

Using genome-editing proteins known as TALENs researchers introduced this single-letter mutation into human red blood cells. TALENs can be designed to cut a gene at a specific point as well as providing the desired piece of donor DNA for insertion.

“Breaks in DNA can be lethal to cells, so they have in-built machinery to repair any nicks as soon as possible, by grabbing any spare DNA that seems to match – much like you might darn a red sock with any spare red wool lying around,” says Professor Crossley.

“We exploited this effect. When our genome editing protein cuts the DNA, the cell quickly replaces it with the donor DNA that we have also provided.”

The team includes researchers from UNSW, the University of Sydney, the University of Melbourne, Murdoch Childrens Research Institute, and Stanford University.

If the genome-editing technique is shown to work effectively in blood stem cells and be safe, it would offer significant advantages over other approaches, such as conventional gene therapy, in which viruses are used to ferry healthy genes into a cell to replace the defective ones.

The genetic changes to cells would not be inherited, making the approach very different to recent controversial Chinese research in which the DNA of human embryos was altered.