US researchers re-engineer CRISPR-Cas9 system to minimize gene editing errors

Crispr-Cas9 is a DNA cutting and pasting system and by tweaking the system the scientists claim they can safely and accurately edit human genes for curing inherited or genetic diseases.

Cas9 enzyme is the key element of the system in the molecular-editing system which claimed to help alter particular DNA sequences in the genome.

The improvement in the CRISPR-Cas9 system can help precise targeted modification in a cell’s DNA. The protein Cas9 changes the DNA at a location that is specified by a short RNA whose sequence is similar that of the target site.

In some cases, the Cas9 system can bind to and reduce additional sites that are not targeted, resulting in the production of unwanted edits that can change gene expression or knock a gene out entirely.

In the study, the researchers used knowledge about the structure of the Cas9 protein to lower off-target cutting.

The scientists experimented with several potential changes and found that mutations in three amino acids dramatically reduced off-target cuts.

The newly-engineered enzyme is called enhanced S. pyogenes Cas9, or eSpCas9. It can be used in genome editing applications that need a high level of specificity, scientists said.

Feng Zhang, one of the researchers, said: "Many of the safety concerns are related to off-target effects.

"We hope the development of eSpCas9 will help address some of those concerns, but we certainly don’t see this as a magic bullet. The field is advancing at a rapid pace, and there is still a lot to learn before we can consider applying this technology for clinical use."

Image: Scientists used structural knowledge of Cas9 to guide engineering of a highly specific genome editing tool. Photo: courtesy of Ian Slaymaker, Broad Institute of MIT and Harvard.