A new class of CRISPR-based tools efficiently corrects point mutations in cell lines, animal models and perhaps the clinic.
When Xingxu Huang began thinking about correcting disease-causing mutations in the human genome, his attention turned naturally to CRISPR–Cas9. But it quickly became clear that the popular gene-editing tool wasn’t ideal for the majority of human disease mutations, which result from errors in single DNA nucleotides known as point mutations. More than 31,000 such mutations in the human genome are known to be associated with human genetic diseases. But CRISPR is not particularly efficient at correcting them.
Then Huang learnt about base editors, a new class of genome-modifying proteins that excel at single-site mutations.
Base editors chemically change one DNA base to another without completely breaking the DNA backbone. The first cytosine base editor (CBE), which chemically converts a cytosine–guanine (C–G) base pair into a thymine–adenine (T–A) base pair at a targeted genomic location, was developed in 2016 by chemical biologists David Liu and Alexis Komor at Harvard University in Cambridge, Massachusetts1. Another researcher in Liu’s laboratory, Nicole Gaudelli, developed the first adenine base editor (ABE) a year later2; it chemically transforms A–T to G–C base pairs.
“Base editing gives very, very good efficiency, about 40–50% efficiency for cell lines,” says Huang, a geneticist at ShanghaiTech University in China. “That’s very high efficiency compared with traditional genome editing,” which is only one-tenth as efficient, he says.
Read more at Nature…