Advancing gene editing with the new CRISPR / Cas9 variant

Using a new variant to repair DNA will improve both the safety and effectiveness of the much-touted CRISPR-Cas9 tool in genetic research, according to researchers at Michigan Medicine.

These two key issues – safety and efficacy – are what continue to hold CRISPR-Cas9 gene targeting to its full clinical potential, says co-lead author Y. Eugene Chen, MD, Ph.D., professor of internal medicine , cardiology surgery, physiology, pharmacology, and medicinal chemistry, Michigan Medicine Frankel Cardiovascular Center.

The new CRISPR-Cas9 variant improves efficiency when inserting a gene or DNA fragment at a precise location in the genome, known as knocking. It also reduces the rate of unintentional insertions or deletions, called indels, of base pairs that often occur in gene changes.

“We call it Meticulous Integration Cas9, or miCas9, to reflect its extraordinary ability to enable maximum integration, but with minimum indels, as well as to recognize its development at the University of Michigan,” write lead authors Chen , Jifeng Zhang and Jie Xu for Nature“Behind the Paper” series. “It provides a ‘one small stone for three birds’ tool in gene editing.”

The team had previously reported the modification of the Cas9 genome in 2014 and reported the beneficial effects of a RAD51 agonist, RS-1, in gene editing in 2016.