Prime editing may have the ability to revert mutated hemoglobin genes back to normal in sickle cell disease (SCD) patient cells and produce normal blood results after cells are transplanted into mice.
This is according to a study conducted by scientists at St. Jude Children’s Research Hospital in New York, New York, and the Broad Institute of MIT and Harvard in Cambridge Massachusetts. The research was published in Nature Biomedical Engineering.
“Prime editing is a promising approach because, in theory, we can directly correct disease mutations to specific healthy DNA sequences of our choosing,” said Jonathan Yen, PhD, of the St. Jude Department of Hematology. “We optimized prime editing in long-term blood stem cells and showed that the prime editing cells maintain full engraftment efficiency in an animal with a clinically relevant system.”
In this study, the researchers edited red blood cells from 4 patients with SCD and transplanted them into mice. They found normal hemoglobin production in approximately 45% of the transplanted cells, even after 17 weeks. Moreover, when the red blood cells isolated from the mouse bone marrow were placed in low-oxygen environments, the sickling was reduced from about 67% to 37%.
“These results show efficient prime editing of blood stem cells and that the prime-edited cells maintain their full ability to engraft and repopulate the bone marrow of an animal,” said David Liu, PhD, the Richard Merkin Professor at the Broad Institute. “Bringing the ‘search-and-replace’ versatility of prime editing to blood stem cells raises the possibility of applying this technology to treat a wide range of diseases involving blood cells.”
Read more about SCD therapies
Safety concerns are always associated with novel genomic editing technologies. Although the researchers found virtually no off-target prime editing, the approach could have unforeseen safety issues. However, it may also be superior to current genome editing methods used in clinical trials, such as Cas9 nucleases, as it doesn’t create double-stranded breaks in DNA.
The new approach also carries its limitations. Prime editing is a long process that requires scientists to adjust each step of the protocol, including the design of the prime editing guide RNAs.
Prime editing shows proof of concept for treating sickle cell disease. News release. St. Jude Children’s Research Hospital; April 17, 2023.