DISCOVERY of a small, deleted region of the genome in patients of sickle cell disease has allowed researchers to use clustered regularly interspaced short palindromic repeats (CRISPR) gene editing to facilitate the persistent expression of fetal globin, which in turn can mitigate the disease. Associate Professor Kate Quinlan, one of the lead researchers of the team at the University of New South Wales (UNSW), Australia, explained that “the persistent expression of fetal globin effectively compensates for the defective adult globin, but up until this piece of research, we didn’t really understand the process that led to this incredible advantage.”
Quinlan stressed the importance of this research: “Sickle cell disease and β-thalassaemia, a closely related disease, are inherited genetic conditions that affect red blood cells. They are fairly common worldwide: over 318,000 infants with these conditions are born every year, and haemoglobin disorders cause 3% of deaths in children aged under 5 years worldwide.” Understanding how to reverse the turning-off of fetal globin is imperative, where a shift to adult globin results in an onset of symptoms as defective red blood cells are introduced. She also shared the mission of their investigation: “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.” This was achieved by a comparison of the deletions in families with a beneficial mutation that protected them from their sickle cell symptoms. Sarah Topfer, a PhD student who conducted the analysis and compiled the data, discovered the use of shared deletion-guided CRISPR gene editing to create this same deletion in the lab artificially. Quinlan stated, “Effectively, by deleting the adult globin ‘on-switch’, we made the fetal globin ‘on-switch’ active.”
Co-leading the research, Professor Merlin Crossley, the Deputy Vice-Chancellor at UNSW, highlighted that “the CRISPR gene editing revolution is accelerating scientific understanding and will deliver new therapies,” spotlighting the potential of this avenue of therapy. The findings from this research have advanced understanding significantly, which is encouraging for patients with blood disorders as this is already informing clinical trials. Since Quinlan described their advances as “a key piece of the puzzle,” it will be interesting to follow how this knowledge translates into practice.