chRDNA technology
Next-generation CRISPR technology
Since the invention of CRISPR-mediated genome editing, a key bottleneck to a broader use of first-generation CRISPR in therapeutics has been specificity. Caribou scientists took on the challenge to improve CRISPR genome-editing precision and invented chRDNA (CRISPR hybrid RNA-DNA, pronounced "chardonnay"). We discovered that adding DNA to the typically all-RNA CRISPR guides significantly improves the precision of genome edits.
Improved specificity is achieved through greatly reduced binding of the chRDNA guide to off-target sequences. Mismatches between off-target sites and the chRDNA guide prevent stable binding of the Cas complex and therefore impair cutting by the Cas nuclease. The chRDNA technology therefore results in a significant reduction in off-target editing.