Iterative Engineering and Optimization Strategies for Maximizing LNP-mediated Gene Editing in the Liver

Optimizing editing potency in target tissues is critical for clinical success of gene editing therapeutics.  This presentation provides an overview of ElevateBio’s strategies to increase in vivo potency of lipid nanoparticle (LNP)-delivered gene editors in the liver of both mice and NHPs. These strategies highlight drug substance and protein engineering approaches across multiple modalities of editing. Importantly, the learnings from these optimizations can ‘feedforward’ to shorten the path to a high potency drug product. Following pharmacologically active editing in NHPs, we were able to quickly identify editors developed in parallel from our platform that further increased in vitro potency by 2-fold.