|By Tyler MacDonald | 1 year ago|
Although many researchers and scientists have high hopes for CRISPR-Cas9 gene editing, they still have plenty to learn about how it works in humans. Take a recent University of California, Berkeley study for instance: the team revealed that people’s assumptions about how cells repair themselves following the DNA snip by the Cas9 enzyme are wrong.
The new discovery sheds light on why CRISPR-Cas9 gene editing works in most cells, but not with equal levels of success. Not only that, but it could help researchers find a way to increase the efficiency of the DNA insertion process.
“If you want to treat sickle cell anemia, your chances of success are inextricably tied to the efficiency with which you can replace the mutated sickle cell gene with the correct one,” said Chris Richardson, first author of a paper. “If you harvest a million cells from a patient and you have 10 percent insertion rate, that is not as good as if you have 30 to 40 percent. Being able to manipulate those cells to increase the frequency of this process, called homology-directed repair, is exciting.”
“Gene editing is super-powerful, with a lot of promise, but, so far, a lot of trial and error. The way it works in human cells has been a black box with a lot of assumptions,” said lead author Jacob Corn. “We are finally starting to get a picture of what’s going on.”
The results revealed that the Fanconi anemia pathway is an important part of gene editing. Although the pathway has been known and examined for decades, it was believed to only edit DNA with a particular kind of DNA damage: interstrand crosslinks.
“Based on our work, we believe that the Fanconi anemia pathway plays a major role in fixing other types of lesions as well, but is best understood as the pathway that repairs double-strand breaks,” Richardson said. “After Cas9 editing, the Fanconi anemia pathway is required if you want to insert new DNA.”
The findings were published in Nature Genetics.