Engineering Cas9 for Editing the Brain

In a new paper in Nature Communications, IGI postdoc Kai Chen and colleagues in the Doudna lab made advances in genome editing in the mouse brain. Their goal was to engineer a Cas9 protein that can be delivered directly to the brain without having to be packaged into a virus or lipid nanoparticle — in other words, a Cas9 protein that is engineered for self delivery.

To meet this goal, Chen and the Doudna lab team screened small cell-penetrating peptides of about 20 amino acids each in brain stem cells from mice. After further engineering the top candidate, they were able to get dramatically improved editing efficiency in the mouse striatum. This brain region is key for a number of neurodegenerative disorders, including Parkinson’s disease and Huntington’s disease. Read the paper here. 

And stay tuned! Moving forward, the team is continuing to expand RNP delivery and gene editing with different tissue targets in collaboration with the Murthy lab.

By Hope Henderson

Hope Henderson holds a B.A. in Biology from Brown University and a Ph.D. in Molecular & Cell Biology from the University of California, Berkeley. She joined the IGI in 2019 to work in science communication. In addition to serving as IGI’s main writer, she plans content strategy and manages IGI’s social media, illustration, and translation.