Engineering Potency And Specificity Of Base Editors Towards Genomic Medicine

By Ron Chong, Vice President, Technology

Cutting‑edge innovations in genome‑editing technologies are advancing therapeutic precision, potency, and safety. A broad suite of editing modalities—spanning nuclease, base, reverse‑transcriptase–based, and epigenetic editing—is powered by an extensive dataset containing millions of CRISPR systems and billions of proteins, enabling deep AI‑driven discovery and optimization. Distinct CRISPR systems occupying unique sequence spaces are engineered for high performance, including expanded PAM recognition across all 264 possible variants to maximize targeting flexibility.

Engineering strategies such as directed evolution, structure‑guided redesign, and iterative screening across cell‑free, bacterial, and mammalian platforms strengthen nickase and deaminase domains while reducing bystander and off‑target editing. Additional workflow enhancements include tuning editing windows, optimizing gRNA architecture, and refining protein domains to achieve target‑specific gains in activity and specificity.

Together, these advances create a comprehensive, end‑to‑end framework for building safer, more potent genome‑editing medicines and rapidly identifying optimal candidates for diverse therapeutic applications.