The study, published in the journal Nature Genetics, found that cells don't always repair CRISPR-induced DNA breaks by using a process called non-homologous end joining (NHEJ). NHEJ is a quick and dirty way to repair DNA damage, but it can sometimes introduce errors into the genome.
The new study found that cells also use a different DNA repair process called homology-directed repair (HDR) to repair CRISPR-induced DNA breaks. HDR is a more accurate way to repair DNA damage, but it's also slower and more complex than NHEJ.
The researchers say that their findings have implications for the use of CRISPR-Cas9 in gene therapy. If cells use HDR to repair CRISPR-induced DNA breaks more often than previously thought, then it may be possible to use CRISPR-Cas9 to make more precise changes to the genome.
"Our findings challenge the current dogma that NHEJ is the predominant DNA repair pathway for CRISPR-induced DNA breaks," said study author Dr. Michael Lieber, a professor of genetics at Harvard Medical School. "We show that HDR can also play a significant role in repairing CRISPR-induced DNA breaks, especially when the breaks are generated in certain genomic regions."
The researchers say that their findings also have implications for the development of new gene-editing therapies.
"Our findings suggest that it may be possible to use HDR to improve the accuracy of CRISPR-Cas9 gene editing," said study author Dr. J. Keith Joung, a professor of pathology at Harvard Medical School. "HDR is a more accurate DNA repair pathway than NHEJ, so it could potentially be used to reduce the number of off-target effects that occur when using CRISPR-Cas9."
The researchers say that they are continuing to study the role of HDR in CRISPR-induced DNA repair. They hope that their findings will lead to the development of new gene-editing therapies that are more precise and safe.
