We are developing unique genome editing molecules to enable predictable, efficient, tissue- and site-specific editing outcomes. We are using both topological and mutagenesis approaches to protein engineering to evolve CRISPR variants with unique properties, such as the ability to sense cellular or environmental signals or different architectures that may allow for greater use of viral vectors or to manipulate the outcomes of editing events. We will deliver our advanced CRISPR-Cas molecules virally or as RNPs. These tools will provide researchers and medical professionals with efficient methods to alter the genome in a precise manner, affording new avenues to treat human disease.