Genome therapy could lead to new treatment for life-threatening blood disorders

July 17, 2017
Credit: CC0 Public Domain

Genome therapy with beneficial natural mutation could lead to new treatment for life-threatening blood disorders

By introducing a beneficial natural mutation into blood cells using the gene-editing technique CRISPR, a UNSW Sydney-led team of scientists has been able to switch on production of foetal - an advance that could eventually lead to a cure for sickle cell anaemia and other .

People with thalassaemia or have damaged adult haemoglobin - the vital molecule that picks up oxygen in the lungs and transports it around the body - and they require life-long treatment with blood transfusions and medication.

However, people with these diseases who also carry the beneficial natural mutation - known as British-198 - have reduced symptoms, because the mutation switches on the foetal haemoglobin gene that is normally turned off after birth.

The extra foetal haemoglobin in their blood, which has a very strong affinity for oxygen, does the work of the defective adult haemoglobin.

"With CRISPR gene-editing we can now precisely cut and alter single within our vast genome," says study senior author and UNSW molecular biologist Professor Merlin Crossley.

"Our laboratory has shown that introducing the beneficial mutation British-198 into using this technology substantially boosts their production of foetal haemoglobin.

"Because this mutation already exists in nature and is benign, this 'organic gene therapy' approach should be effective and safe to use to treat, and possibly cure, serious blood disorders. However, more research is still needed before it can be tested in people," he says.

The study by scientists from UNSW, the Japanese Red Cross Society and the RIKEN BioResource Centre in Japan, is published in the journal Blood.

The beneficial British-198 mutation, which was first identified in a large British family in 1974, involves a change in just a single letter of the genetic code.

Carriers of this mutation have foetal haemoglobins levels as high as 20 per cent of total haemoglobin, while most people's foetal haemoglobin levels fall to about 1 per cent of total haemoglobin after birth.

The researchers also discovered how this British-198 mutation works. They found it creates a new binding site for a protein called KLF1 that turns blood genes on.

Mutations affecting adult haemoglobin production are among the most common of all genetic variations, with about 5 per cent of the world's population carrying a defective gene.

"To turn the new gene editing approach into a therapy for blood disorders, the British-198 mutation would have to be introduced into blood-forming stem cells from the patient," says Professor Crossley.

"A large number of stem cells would have to be edited in order to repopulate the patients' with genetically enhanced ."

The video will load shortly

Explore further: New age of genome editing could lead to cure for sickle cell anemia

More information: Beeke Wienert et al, KLF1 drives the expression of fetal hemoglobin in British HPFH, Blood (2017). DOI: 10.1182/blood-2017-02-767400

Related Stories

New age of genome editing could lead to cure for sickle cell anemia

May 14, 2015
UNSW Australia researchers have shown that changing just a single letter of the DNA of human red blood cells in the laboratory increases their production of oxygen-carrying haemoglobin - a world-first advance that could lead ...

One day, science may cure sickle cell anaemia

July 9, 2014
Genetic mutations that affect our blood cells' haemoglobin are the most common of all mutations. It has been estimated that around 5% of the world's population carry a defective globin gene.

The slow climb from innovation to cure—treating anaemia with gene editing

October 19, 2016
The ability to precisely edit DNA via CRISPR technology has emerged as the one of the most powerful advances in biology. A new paper showing repair of a genetic mutation in human blood cells represents an important step towards ...

Scientists repair gene defect in stem cells from patients with rare immunodeficiency

January 11, 2017
Scientists have developed a new approach to repair a defective gene in blood-forming stem cells from patients with a rare genetic immunodeficiency disorder called X-linked chronic granulomatous disease (X-CGD). After transplant ...

Scientists edit gene mutations in inherited form of anemia

October 26, 2016
A Yale-led research team used a new gene editing strategy to correct mutations that cause thalassemia, a form of anemia. Their gene editing technique provided corrections to the mutations and alleviated the disease in mice, ...

Timing of mutation determines the outcome

June 30, 2017
A single genetic mutation can lead to completely different diseases, depending on the time and location at which the mutation occurs. This finding emerged from the PhD study conducted by Rocio Acuña-Hidalgo of Radboudumc. ...

Recommended for you

Scientists identify new way cells turn off genes

July 19, 2017
Cells have more than one trick up their sleeve for controlling certain genes that regulate fetal growth and development.

South Asian genomes could be boon for disease research, scientists say

July 18, 2017
The Indian subcontinent's massive population is nearing 1.5 billion according to recent accounts. But that population is far from monolithic; it's made up of nearly 5,000 well-defined sub-groups, making the region one of ...

Mutant yeast reveals details of the aberrant genomic machinery of children's high-grade gliomas

July 18, 2017
St. Jude Children's Research Hospital biologists have used engineered yeast cells to discover how a mutation that is frequently found in pediatric brain tumor high-grade glioma triggers a cascade of genomic malfunctions.

Late-breaking mutations may play an important role in autism

July 17, 2017
A study of nearly 6,000 families, combining three genetic sequencing technologies, finds that mutations that occur after conception play an important role in autism. A team led by investigators at Boston Children's Hospital ...

Newly discovered gene variants link innate immunity and Alzheimer's disease

July 17, 2017
Three new gene variants, found in a genome wide association study of Alzheimer's disease (AD), point to the brain's immune cells in the onset of the disorder. These genes encode three proteins that are found in microglia, ...

Newly identified genetic marker may help detect high-risk flu patients

July 17, 2017
Researchers have discovered an inherited genetic variation that may help identify patients at elevated risk for severe, potentially fatal influenza infections. The scientists have also linked the gene variant to a mechanism ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.