‘Waking Up’ Fetal Hemoglobin To Treat Blood Disorders

Researchers have demonstrated that gene editing can be used to re-introduce a fetal form of hemoglobin, thereby treating sickle cell anemia.

AsianScientist (May 19, 2015) – Changing just a single letter of the DNA of human red blood cells in the laboratory increases their production of oxygen-carrying hemoglobin, according to a study published in Nature Communications. The discovery, by Professor Merlin Crossley and PhD student Mr. Beeke Wienert at the University of New South Wales, could lead to a treatment for sickle cell anemia and other blood disorders.

The new genome editing technique, in which a beneficial, naturally-occurring genetic mutation is introduced into cells, works by switching on a sleeping gene that is active in the womb but turned off in most people after birth.

“An exciting new age of genome editing is beginning, now that single genes within our vast genome can be precisely cut and repaired,” says Crossley.

Crossley elaborated on the details of the study, which could help people with damaged hemoglobin.

“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 anemia and thalassaemia—inherited diseases in which people have damaged hemoglobin.”

“Because the good genetic variation we introduced already exists in nature, this approach should be effective and safe. However, more research is needed before it can be tested in people as a possible cure for serious blood diseases.”

People produce two different kinds of hemoglobin–the vital molecule that picks up oxygen in the lungs and transports it around the body.

“During development in the womb, the fetal hemoglobin gene is switched on. This produces fetal hemoglobin, which has a high affinity for oxygen, allowing the baby to snatch oxygen from its mother’s blood,” says Crossley.

“After we are born, the fetal hemoglobin gene is shut off and the adult hemoglobin gene is switched on.”

Mutations affecting adult hemoglobin are among the most common of all human genetic mutations, with about five percent of the world’s population carrying a defective adult hemoglobin gene.

People who inherit two mutant genes–one from their mother and one from their father–have damaged hemoglobin and suffer from life-threatening diseases such as sickle cell anaemia and thalassaemia, which require life-long treatment with blood transfusions and medication.

The researchers based their new approach on the fact that a small number of people with damaged adult hemoglobin have an additional, beneficial mutation in the fetal hemoglobin gene.

“This good mutation keeps their fetal hemoglobin gene switched on for the whole of their lives and reduces their symptoms significantly,” says Crossley.

The researchers introduced this single-letter mutation into human red blood cells using genome-editing proteins known as TALENs, which 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 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.”

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.

The article can be found at: Wienert et al. (2015) Editing The genome To Introduce A Beneficial Naturally Occurring Mutation Associated With Increased Fetal Globin.

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Source: The University of New South Wales.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

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