Illustration of DNA ligase, one of the cell proteins involved in repairing double-strand breaks in DNAWIKIMEDIA; WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS, TOM ELLENBERGERMost genetic diseases in humans are caused by point mutations—single base errors in the DNA sequence. However, current genome-editing methods cannot efficiently correct these mutations in cells, and often cause random nucleotide insertions or deletions (indels) as a byproduct. Now, researchers at Harvard University have modified CRISPR/Cas9 technology to get around these problems, creating a new “base editor,” described today (April 20) in Nature, which permanently and efficiently converts cytosine (C) to uracil (U) bases with low error in human and mouse cell lines.
“There are a lot of genetic diseases where you would want, in essence, to swap bases in and out,” said Jacob Corn, scientific director of the Innovative Genomics Initiative at the University of California, Berkeley, who was not involved in the research. “Trying to get this to work is one of the big challenges in the field, and I think this is a really exciting approach.”
To date, CRISPR/Cas9 genome-editing approaches have relied on a cellular mechanism called homology-directed repair, which is triggered by double-strand breaks in DNA. Researchers supply cells with a template containing the desired sequence, make a targeted double-strand break with the Cas9 enzyme, and then wait to see whether homology-directed repair incorporates the template to reconnect the strands. Unfortunately, this method ...
