CRISPR/Cas9 gene activation 'guide' could lead to new therapies

CRISPR/Cas9 gained prominence as a tool to edit DNA but is increasingly being recognized for its ability to activate gene expression. Scientists from Harvard University’s Wyss Institute created a “guide” to gene-activating Cas9 proteins, which could help bioengineers develop more effective targeted gene therapies.

While a number of synthetic gene-activating Cas9 proteins have been tested in selectively activating genes, a guide comparing the proteins’ relative potentials didn’t exist, said George Church of the Wyss Institute in a statement. So the Wyss team compared and ranked the most commonly used synthetic Cas9 activators in different cell types from multiple species, including humans, mice and flies. The resulting report, published Monday in Nature Methods, could help other researchers streamline their efforts to develop gene-activating Cas9 proteins as therapies for conditions that involve insufficient gene expression.

"We first surveyed seven advanced Cas9 activators, comparing them to each other and the original Cas9 activator that served to provide proof-of-concept for the gene activation potential of CRISPR-Cas9,” said Marcelle Tuttle, research fellow at the Wyss Institute, in a university news release. “Three of them, provided much higher gene activation than the other candidates while maintaining high specificities toward their target genes." The team also identified methods to maximize gene activation using these top three candidates.

"The ease of use of CRISPR-Cas9 offers enormous potential for development of genome therapeutics," said Dr. Donald Ingber, Wyss Institute founding director, in the statement. "This study provides valuable new design criteria that will help enable synthetic biologists and bioengineers to develop more effective targeted genome engineering technologies in the future."

CRISPR/Cas9 has been taking the biotech world by storm, with a slew of companies making big bets on the technology. These include gene-editing companies Intellia Therapeutics ($NTLA) and Editas ($EDIT), which are both based in Cambridge, MA, and had their IPOs this year, as well as Bayer, which dropped $335 million on a JV with CRISPR Therapeutics late last year.

- here's the statement
- here's the study abstract