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.
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.
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.
“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
