[E-Daily Reporter NA EUN-KYUNG ] Genomictree Inc.(228760)has developed a lipid nanoparticle (LNP) technology that delivers messenger RNA (mRNA) to the brain and spinal cord via intravenous injection without the need for a separate targeting agent.

Genomictree Inc. announced on the 15th that it has developed and filed a patent application for an LNP platform technology capable of delivering mRNA to the central nervous system (CNS), and that a related research paper has been accepted for publication in the international academic journal *ACS Materials Letters*.

LNPs are carriers that protect mRNA within the body and deliver it to cells. Conventional LNPs administered intravenously tend to accumulate primarily in the liver, limiting their ability to deliver mRNA to tissues other than the liver. In particular, the brain and spinal cord are considered tissues where it is difficult to deliver therapeutic agents via systemic administration due to the presence of the blood-brain barrier (BBB) and the blood-spinal cord barrier (BSCB).

To address this, researchers are exploring methods to attach target ligands—such as antibodies or peptides—to the surface of LNPs; however, this can lead to more complex formulations and manufacturing processes. Instead of adding a separate target ligand, Genomictree Inc. opted to adjust the types and concentrations of the lipids that make up the LNP.

Genomictree Inc.’s research team had previously developed and filed a patent application for an LNP formulation that replaces cholesterol—a major component of conventional LNPs—with protopanaxadiol (PPD), a key structural component of ginsenosides, or ginsenoside Rg2. In this study, they added phosphatidylserine (PS)—a type of phospholipid that makes up cell membranes—to this formulation and evaluated how the location of mRNA delivery and the extent of expression varied depending on the PS content.

The results showed that LNPs containing low levels of PS increased mRNA delivery and expression in cells associated with the central nervous system. When the research team loaded mRNA encoding the luminescent enzyme luciferase (Luc) into LNPs and administered them intravenously to mice, the group treated with PS-containing LNPs exhibited higher Luc expression in the brain and spinal cord compared to the control group without PS.

Luc expression was also confirmed in excised brain and spinal cord tissues. The company explained that these results demonstrate that systemically administered LNPs not only reach central nervous system tissues but also achieve “functional expression,” in which the mRNA carried by the LNPs is actually translated into protein.

Differences in the tissues targeted by the LNP were also observed depending on the PS content. When the PS content was increased from 1 mol% to 4 mol%, mRNA expression decreased in the brain but increased in the spleen. The 1 mol% PS-PPD-LNP exhibited approximately 1.45 times higher Luc expression in the brain compared to the 4 mol% formulation, whereas the 4 mol% formulation showed approximately 1.9 times higher expression in the spleen.

The research team plans to further investigate the potential of utilizing the brain and spinal cord delivery characteristics observed at low PS concentrations for the development of mRNA therapeutics for central nervous system (CNS) diseases. They believe that the spleen and lymphoid tissue targeting observed at high PS concentrations could be applied in the development of cancer vaccines or immunotherapies that deliver mRNA to immune cells.

However, this study is a preclinical study using mice and other models. To actually apply this technology to the treatment of central nervous system disorders, follow-up studies are needed to elucidate the delivery pathways and mechanisms of action of LNPs into the central nervous system, load them with therapeutic mRNA, and verify therapeutic efficacy in disease models.

Ahn Seong-hwan, CEO of Genomictree Inc., stated, “By designing the lipid composition of the LNP, we confirmed the potential to induce functional mRNA expression in the brain and spinal cord following systemic administration without the need for a separate targeting ligand,” adding, “We also confirmed that different distribution characteristics are observed in the central nervous system and spleen and lymphatic tissues depending on the PS content.”

He added, “Going forward, we plan to specifically elucidate the central nervous system delivery pathways and mechanisms of action, and conduct efficacy studies using therapeutic mRNA and mRNA for anti-cancer immunotherapy.”