Leveraging protein and gRNA engineering of diverse CRISPR systems to optimize adenosine base editor activity for correction of a causative monogenic disease mutation

This presentation details a systematic approach to optimize an adenosine base editor (ABE) for correcting a specific disease-causing genetic mutation (a G>A SNP). Through parallel engineering of both the editor protein and its guide RNA (gRNA), we achieved a substantial increase in potency, increasing editing efficiency from an initial ~10% to over 85%. These modifications also enhanced specificity, minimizing unwanted edits at nearby "bystander" sites and reduced detectable "off-target" effects to nearly zero.