Study uses gene editing to take brakes off lab-based red blood cell production

Turning off a single gene leads to a roughly three-to-five-fold gain in the yield of laboratory methods for producing red blood cells from stem cells, according to a multi-institutional team led by researchers at Dana-Farber/Boston Children's Cancer and Blood Disorders Center.

These findings, published in Cell Stem Cell, suggest a way to cost-effectively manufacture red blood cells from stem cells; the patients who could potentially benefit include those who cannot use blood currently available in blood banks.

Previous research has shown that it is possible to use various methods to force different kinds of stem cells to produce transfusion-grade red blood cells in a laboratory, but, at a cost between $8,000 and $15,000 per unit of blood, the processes are expensive. This is the first study to combine stem cells, powerful gene editing tools, and data from genome-wide association studies (GWAS).

The research team behind the Cell Stem Cell study--led by senior author and Dana-Farber/Boston Children's pediatric hematologist Vijay Sankaran, MD, PhD--homed in on their target gene, called SH2B3, after GWAS data revealed naturally occurring variations in the gene's sequence that reduce its activity result in increased red blood cell production.

"There's a variation in SH2B3 found in about 40 percent of people that leads to modestly higher red blood cell counts," Sankaran said. "But if you look at people with really high red blood cell levels, they often have rare SH2B3 mutations. That said to us that here is a target where you can partially or completely eliminate its function as a way of increasing red blood cells robustly.