Hepa-SENSTM: Development of a Hepatocyte-Selective mRNA Delivery Platform Overcoming LDLR Dependence.

Goo-Yong Kim – Team leader, Samyang Biopharm; Sojin Lee – Team leader, Samyang Biopharm; Hyosuk Kim – Senior researcher, Samyang Biopharm; Hyejin Park – Senior researcher, Samyang Biopharm; Yisak Kim – Senior researcher, Samyang Biopharm; Jihye Choi – Senior researcher, Samyang Biopharm; Jongmin Kim – Senior researcher, Samyang Biopharm; Jongmin Park – Senior researcher, Samyang Biopharm; Joungpyo Nam – Senior researcher, Samyang Biopharm; Wonil Seo – Senior researcher, Samyang Biopharm; Helen Cho – Head of Biopharmaceutical R&D, Samyang Biopharm

Introduction:

An effective RNA therapeutic delivery system must ensure consistent performance across both healthy and diseased liver conditions, support repeat dosing without inducing toxicity, and minimize immunogenic responses. Clinically validated hepatocyte receptors—low-density lipoprotein receptor (LDLR) and asialoglycoprotein receptor (ASGPR)—support approved therapies such as patisiran (Onpattro) and inclisiran (Leqvio). Given the disease-sensitive and relatively low expression of LDLR compared to the robust, disease-resilient expression of ASGPR, ASGPR-mediated delivery presents a compelling strategy.