Pre-Conference Day

Chemical engineering of RNAi therapeutics is pivotal for expanding their delivery beyond the liver, to tissues like the CNS, muscle, and eye. Attendees will gain insights into optimizing RNAi constructs for improved stability,

potency, and delivery efficiency, bridging the gap between preclinical promise and clinical success. A must-attend for researchers aiming to unlock the full potential of RNAi in extrahepatic applications by discussing:

• Incorporating phosphorothioate and 2-modifications to boost siRNA nuclease resistance, enabling prolonged activity in extrahepatic tissues
• Designing lipid-conjugated siRNAs for enhanced cellular uptake without carriers, simplifying delivery to challenging targets like skeletal muscle or the eye
• Tailoring hydrophobicity and charge to optimize biodistribution and endosomal escape, maximizing target gene knockdown in non-liver organs

The rapid evolution of in silico tools is revolutionizing RNAi therapeutic development, from target discovery to regulatory approval. Attendees will learn how to leverage these tools to expand RNAi applications beyond

current frontiers, optimize drug stability, and navigate regulatory hurdles. A must for teams aiming to harness data-driven approaches for faster, smarter RNAi therapeutic design

• Deploying AI-powered genomic and transcriptomic analysis to uncover high-confidence RNAi targets, and directed evolution-based discovery of novel protein-to-protein interactions governing tissue-selective, extrahepatic delivery of siRNA.
• Applying machine learning to predict off-target effects and potency, streamlining lead candidate selection, and reducing late-stage attrition in preclinical development
• Utilizing computational modelling to connect sequence and structure with functional data layers, such as predicting ligands for orphan receptors, binding affinity, internalization dynamics and stability, to accelerate discovery and translation of early leads.