A team from MIT and Harvard developed a new CRISPR genome-editing approach that can make extremely precise DNA edits.
The breakthrough tool, known as prime editing, has the potential to correct up to 89 percent of known disease-causing genetic variations.
“A major aspiration in the molecular life sciences is the ability to precisely make any change to the genome in any location. We think prime editing brings us closer to that goal,” senior study author David Liu, a Broad Institute member, said in a statement.
“We’re not aware of another editing technology in mammalian cells that offers this level of versatility and precision with so few byproducts,” he added.
The first, and arguably most well-known, CRISPR genome editing tool was the Cas9 protein, which cuts DNA to alter a cell’s genome.
And, much like base editing builds on that technology, the Broad Institute’s prime editing system couples Cas9 with the reverse transcriptase protein to “prime,” or initiate, the editing genetic information.
A research paper, published this week by the journal Nature, describes the new technique via a series of experiments using four human cell lines and mouse brain cells.
Performing 175 different DNA edits, researchers show how prime editing can change DNA with incredible precision and, importantly, introduces errors at a much lower rate.
“With prime editing, we can now directly correct the sickle-cell anemia mutation back to the normal sequence and remove the four extra DNA bases that cause Tay-Sachs disease, without cutting DNA entirely or needing DNA templates,” according to Liu, a professor of chemistry and chemical biology at Harvard. “The beauty of this system is that there are few restrictions on the edited sequence.”
“The versatility of prime editing quickly became apparent as we developed this technology,” first study author Andrew Anzalone, a postdoctoral fellow in Liu’s lab at the Broad Institute, said. “The fact that we could directly copy new genetic information into a target site was a revelation. We were really excited.”
The CRISPR gene-editing method has been touted as a revolutionary tool to target HIV and autism, change agricultural practices, and, most controversially, curb HIV infection in twin babies.
Chinese scientist He Jiankui’s lab allegedly used the technology to alter the DNA of sisters Lulu and Nana, born in November. A recent study by the University of California, Berkeley, suggested the genetically edited infants are at risk of a 21 percent increase in mortality in later life.
Prime editors, meanwhile, are not designed to take over from CRISPR-Cas9 or base editors. Rather, they should work together, according to Liu.
Moving forward, researchers will continue optimizing prime editing: investigating potential effects, conducting further tests, and exploring delivery mechanisms.
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