DNA clews used to shuttle CRISPR-Cas9 gene-editing tool into cells

Researchers from North Carolina State University and the University of North Carolina at Chapel Hill have for the first time created and used a nanoscale vehicle made of DNA to deliver a CRISPR-Cas9 gene-editing tool into cells in both cell culture and an animal model. 

The CRISPR-Cas system, which is found in bacteria and archaea, protects bacteria from invaders such as viruses. It does this by creating small strands of RNA called CRISPR RNAs, which match DNA sequences specific to a given invader. When those CRISPR RNAs find a match, they unleash Cas9 proteins that cut the DNA.

In recent years, the CRISPR-Cas system has garnered a great deal of attention in the research community for its potential use as a gene editing tool -- with the CRISPR RNA identifying the targeted portion of the relevant DNA, and the Cas protein cleaving it.

But for Cas9 to do its work, it must first find its way into the cell. This work focused on demonstrating the potential of a new vehicle for directly introducing the CRISPR-Cas9 complex -- the entire gene-editing tool -- into a cell.

"Traditionally, researchers deliver DNA into a targeted cell to make the CRISPR RNA and Cas9 inside the cell itself -- but that limits control over its dosage," says Chase Beisel, co-senior author of the paper and an assistant professor in the department of chemical and biomolecular engineering at NC State. "By directly delivering the Cas9 protein itself, instead of turning the cell into a Cas9 factory, we can ensure that the cell receives the active editing system and can reduce problems with unintended editing."