Hokkaido University Research Profiles

Life Sciences

In Vivo Nucleic Acid Delivery System Based on the Development of Unique Functional Lipids

Balancing world-class functional delivery of nucleic acids and safety

We have developed a unique group of functional lipids for the safe and efficient in vivo delivery of siRNA. The lipid nanoparticles containing these lipids showed world-class functional delivery of siRNA in hepatocytes due to their excellent endosomal escape ability and high safety due to their biodegradability.

Content of 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.

Potential for social implementation

  • ・Gene function analysis at the individual animal level
  • ・Nucleic acid drug development

Appealing points to industry and local governments

Since this technology shows efficient delivery of nucleic acids, safety, and a high degree of freedom in formulation properties, delivery of nucleic acids is not limited to siRNA, and the target is not limited to hepatocytes. We would therefore be happy to collaborate on research with companies and research institutions that have specific target cells, target genes, or nucleic acid technologies.

Intellectual property related to this research

特願2017-117708 「siRNA細胞内送達のための脂質膜構造体」