Research

The key to the practical application of siRNA is the development of superior delivery technology, but there is still much room for improvement in the delivery efficiency. In addition, from the viewpoint of practicality, it is also important to secure a wide safe therapeutic window. It is also highly desirable to develop platform technologies that can provide appropriate formulations for different purposes without being limited to specific applications. To achieve these goals, we have developed a unique group of pH-sensitive cationic lipids. We achieved the modulation of acid dissociation constants, which is an important factor for the pharmacokinetics of lipid nanoparticles, enabling a target-specific molecular design. The lipid nanoparticles containing the novel lipid CL4H6 induced gene silencing in hepatocytes with world-class efficiency. No significant hepatotoxicity was also observed even after the administration of approximately 3,000-fold higher dose for 50% gene silencing, thus a high level of safety was confirmed. CL4H6 was rapidly degraded and eliminated after siRNA delivery.