CRISPR Reveals the Mechanism Behind Sickle Cell Disease

Using CRISPR gene editing, researchers have investigated new therapeutic approaches for sickle cell disease, one of the world's most devastating genetic blood disorders. The findings of the study are published in the journal Blood.

"Sickle cell disease and beta thalassemia, a closely related disease, are inherited genetic conditions that affect red blood cells," said researcher Kate Quinlan from the University of New South Wales.

Sickle Cell Anemia–Causes-Symptoms-Diagnosis-Treatment–Prognosis
Sickle cell anemia (SCA) is a genetic blood disorder caused by abnormal inherited hemoglobin. Sickle cell anemia is the most common form of sickle cell disease.

‘Sickle cell disease and beta thalassemia are fairly common worldwide -- over 318,000 infants with these conditions are born every year and hemoglobin disorders cause 3 per cent of deaths in children aged under five years worldwide.’

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Genetic mutations, specifically, a defect in the adult globin gene, are responsible for the disorders. The mutant genes affect the production of hemoglobin, the protein in red blood cells that carries oxygen around our bodies.

"Interestingly, when children are born, they do not show disease symptoms at first, even if they have the mutations, because, at that stage, they are still expressing fetal globin and not yet adult globin. That's because we have different hemoglobin genes that we express at different stages of development," Quinlan said.

"As the fetal globin gets turned off, and adult globin gets turned on, which happens within about the first year of life, the symptoms start to manifest," Quinlan added.

Thalassemia - Symptoms, Diagnosis, Treatment, Future Therapies
Thalassemia is an inherited blood disorder passed on through parental genes causing the body to produce abnormal hemoglobin.

When that happens, the red blood cells take on unusual, sickled shapes and block small blood vessels, causing pain, organ damage, and premature death.

"The goal of our research is finding out how we can reverse the fetal to adult globin switch, so that patients continue to express fetal globin throughout life, rather than the mutant adult globin genes that cause blood cells to become stiff and block vessels," said Quinlan.

The Breakthrough of 2015 - CRISPR
CRISPR is a gene editing tool that is revolutionizing medical care with prospective cure for genetic diseases like cancer, diabetes, DMD, eye diseases, obesity.

For the study, the research team compiled data on the rare families that express fetal globin throughout life.

Then, they used CRISPR gene editing to replicate some of these big patient deletions, and the small deleted bit they all had in common, in cell lines in the lab.

Newly Engineered Gene Therapy Offers Safer Treatment For Blood Disorders
Potentially safer and more effective gene therapy vector for blood disorders have been developed.

"CRISPR allows us to 'cut' bits of DNA out of cells grown in the lab, to modify genes and see what happens as a result - it's essentially a tool to figure out what genes do inside living cells," Quinlan said.

"We found that deleting just that one little bit was sufficient to make fetal globin go up and adult globin down, which suggests that we have found the key mechanism that can explain why fetal globin levels remain high in these asymptomatic patients."

Quinlan mentioned that "effectively, by deleting the adult globin 'on switch', we made the fetal globin 'on switch' active".

Source-IANS