Concept image.

CRISPR-Cas9 has brought a revolution in the manipulation of DNA over the last five years. But there are errors made in the process, especially when a cytosine-guanine base pair is mistakenly changed to pairs other than the desired thymine-adenine pair.

But a Harvard team reports that they have devised a new “generation” of DNA editing techniques, which significantly reduces the error and increases efficiency, as they report in the journal Science Advances.

Their discovery was that the unwanted by-products of the C-G base pairs was being fostered by the presence of an enzyme called uracil N-glycosylase (UNG).

The team reports that they added an inhibitor called BE4 to the process of cutting and replacing strands of DNA.

The efficiency of C-G to T-A changes was improved by 50 percent, they report.

The errors were cut in half at the same time, they add.

“By analyzing individual DNA sequencing reads, we discovered that blocking IUNG access to the uracil intermediate is especially crucial for target loci in which a single C is within the editing window to minimize undesired products,” they write.

“Collectively, these developments advance the state of the art in programmable C-G to T-A base pair conversion and thereby increase the utility and applicability of base editing,” they add.

DNA editing has been used in organisms for several years – but is just starting to be explored in humans. The limits to genetic engineering of human cells have not been firmly established, at international or even national levels. The U.S. had not engaged in the kinds of boundary pushing of China and Sweden – until this summer. The first genetic manipulations of human embryos in the U.S. was reported by the Oregon Health and Science University in the journal Nature.