Breakthrough in mRNA Delivery System Safety
Yonsei University researchers have successfully developed a novel mRNA delivery system utilizing electrically neutral self-assembling peptides (ENSPs) to significantly reduce cellular and biological toxicity. Traditional mRNA nanocarriers typically rely on electrostatic attraction between positively charged molecules and mRNA, which has historically posed limitations due to cellular toxicity stemming from cationic properties and surfactant characteristics. To overcome this hurdle, the research team engineered a delivery system using peptides that are electrically neutral and minimize surfactant behavior.
How the New Nanotube mRNA Delivery System Works
According to the research team, ENSPs bind to mRNA through hydrogen bonding and hydrophobic interactions rather than conventional electrical charges, wrapping the mRNA in a spiral to form a stable nanotube structure. In comprehensive cellular and animal experiments, this ENSP-based mRNA delivery system demonstrated robust gene delivery efficiency while exhibiting lower toxicity compared to conventional cationic peptides, lipid nanoparticles, and cationic polymer-based carriers. Furthermore, evaluations measuring echinocyte formationβa red blood cell shape deformation occurring when carriers contact bloodβconfirmed that the ENSP-based carriers displayed lower toxicity than comparison groups.
Implications for Future Therapeutics
Prof. Yongbum Lee noted that substituting cationic molecules with electrically neutral molecules successfully decreases cellular and biological toxicity, laying a strong foundation for developing safe and stable mRNA delivery systems. This cutting-edge study was supported by the Mid-career Researcher Program of the National Research Foundation of Korea, with Ph.D. candidate Jiho Jang participating as the first author. The findings were officially published online on August 22 in the international academic journal Nature Communications.
