Cromwell, CR., et. al. (2018) Nature Communications. 9:1448. https://www.ncbi.nlm.nih.gov/pubmed/29654299
Off-target effects resulting from CRISPR gene editing could hamper the systems adoption as a therapeutic technique. In a recent Nature Communications publication, Cromwell et. al. demonstrate that use of next-generation bridged nucleic acids (BNA) and locked nucleic acids (LNA) at specifics spots in the crRNA can reduce off-target cleavage by multiple orders of magnitude. The authors demonstrate that this is due to the modified nucleic acids slowing Cas9 kinetics.