Base Editing Used to Repair Mutations in Muscle Stem Cells

A joint research collaboration between scientists at the Max Delbruck Center for Molecular Medicine and the Berlin University of Medicine, successfully repaired an SGCA mutation in human primary muscle stem cells using base editing. The loss of function of this gene is related to the development of muscular atrophy. Their findings were published in JCI Insight. 

For the study, the researchers took a sample of muscle tissue from a ten-year-old patient, isolated the stem cells, multiplied these in vitro, and used base editing to replace a base pair at the mutated site. They then injected the edited muscle stem cells into mouse muscles, which can tolerate foreign human cells. These multiplied in the rodent and most developed into muscle fibers. "With this, we were able to show for the first time that it is possible to replace diseased muscle cells with healthy ones," says lead researcher Simone Spuler. Following further tests, the repaired stem cells will be reintroduced to the patient.

Whereas in CRISPR-Cas9 gene-editing both strands of DNA are cut by these molecular scissors, the Cas enzymes used for base editing snip off the residual glucose from a particular base and attach a different one, creating a different base at the targeted site. 

"This tool works more like tweezers than scissors, and is perfect for carrying out targeted point mutations in a gene," says collaborator Helena Escobar. "It is also a much safer method, because unwanted changes are extremely rare. In the genetically repaired muscle stem cells, we have not witnessed any misediting at unintended regions of the genome." Escobar is the study's lead author and the one who developed the technique for the muscle cells.

While autologous cell therapy will not enable sufferers who are already wheelchair-bound to walk again, the study provides the first proof that a form of therapy may even be possible for a group of previously incurable diseases, and it could be used to repair small muscle defects, such as those in the finger flexor.