The therapeutic window of RNAi is defined by the intricate balance between potent silencing and off-target effects, driven by advances in chemical modifications, novel conjugate strategies, and a deeper understanding of RNAi pharmacology. This roundtable convenes experts pioneering these chemical and biological innovations to define the principles for building better, safer RNAi therapeutics by discussing:

• How are novel phosphorothioate patterns, 2’-modifications, and scaffold designs being used to actively direct biodistribution, improve cellular uptake, and facilitate endosomal escape
• Comparing the advantages, limitations, and unique pharmacological profiles of emerging delivery vehicles.
• Integrating predictive tools for immunogenicity and off-target effects early in candidate selection.