New gene editing technology could correct 89% of genetic defects

Scientists have developed a new gene-editing technology that could potentially correct up to 89% of genetic defects, including those that cause diseases like sickle cell anemia.

The new technique is called “prime editing,” and was developed by researchers from the Broad Institute of MIT and Harvard, who published their findings Monday in the journal Nature.

Prime editing builds on powerful CRISPR gene editing, but is more precise and versatile — it “directly writes new genetic information into a specified DNA site,” according to the paper.

In the traditional CRISPR-Cas9 approach, Cas9, a type of modified protein, acts like a pair of scissors that can snip parts of DNA strands. It can target genes in a specific location — for instance, to disrupt a mutation.

About two-thirds of known human genetic variants associated with diseases are single point gene mutations, so gene editing has the potential to correct or reproduce such mutations.

Prime editing combines the CRISPR-Cas9 method with a different protein that can generate new DNA. The tool nicks the DNA strand, then transfers an edited sequence to the target DNA — allowing researchers to smoothly insert and delete parts of human cells.

The technique allows researchers to search and replace entire sections of DNA strands, all without disruptive breaks or donor DNA. With this method, researchers say they hope to accurately and efficiently correct up to 89% of known disease-causing genetic variations.

“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,” said David Liu, one of the authors of the study, in a Broad Institute press release.

“The versatility of prime editing quickly became apparent as we developed this technology,” said Andrew Anzalone, another author in the study, in the press release. “The fact that we could directly copy new genetic information into a target site was a revelation. We were really excited.”

The team of researchers will now continue working to hone the technique, trying to maximize its efficiency in various cell types and exploring any potential effects on the cells. They will also continue testing on different models of diseases to ultimately “provide a potential path for human therapeutic applications,” according to the press release.

Gene editing is still a relatively young and rapidly expanding field of study — CRISPR-Cas9 is based on a decade-old discovery, but was only used on humans for the first time in 2016. Then in 2017, the Broad Institute developed a new technique called base editing, which can make changes to a targeted DNA site without cutting the DNA.

Researchers at the Broad Institute and elsewhere hope CRISPR could one day target a wide range of “bad” genes — potentially helping humans avoid obesity, Alzheimer’s disease, genetic forms of deafness, and more.

However, as the technology has advanced, doctors, scientists, and bioethicists have also raised ethical questions. Some fear it could open the door to human embryos being manipulated for nontherapeutic reasons, or that it could create unintended mutations and new diseases.

Just earlier this year in March, a group of researchers, including the scientist who pioneered and patented CRISPR technology, called for a global moratorium on human germline editing — changes made to inherited DNA that can be passed on to the next generation.

They listed ethical concerns, and pointed to Chinese scientist He Jiankui, who claimed to have made gene edits when creating two AIDS-resistant babies last year. He’s work, which could have unforeseen consequences, has been internationally condemned and called “abominable in nature” by Chinese authorities.