Notwithstanding these advances, several challenges remain for CRISPR nucleases to be broadly useful for interrogating and correcting disease-relevant sequences. Notably, Cas enzymes remain unable to efficiently discriminate intended from unintended sequences that differ by small sequence changes, and the intended ‘edit-outcome' is often not achievable at requisite frequencies. The central focus of the Kleinstiver laboratory is therefore to leverage naturally occurring and engineered CRISPR enzymes to more effectively model and treat disease, by:1) Engineering CRISPR enzymes capable of single nucleotide discrimination
2) Tailoring genome editing reagents for the detection and correction of unique genetic sequences
3) Developing protein engineering strategies to further improve properties of genome editing enzymes