△ (From left) Professor Koo Hee-beom, Dr. Kim Bu-geon, Researcher Park Chul-hee

mRNA technology, which gained global recognition through COVID-19 vaccines, is now drawing attention as a next-generation treatment for cancer and rare diseases. However, mRNA is extremely fragile and easily destroyed within the body. To protect it and deliver it safely into cells, "delivery boxes" known as Lipid Nanoparticles (LNPs) are used.

A joint research team led by Professor Koo Hee-beom (Corresponding Author), Dr. Kim Bu-geon (Co-First Author), and Researcher Park Chul-hee (Co-First Author) from the Department of Biomedicine and Health Sciences at the Catholic University of Korea College of Medicine has scientifically identified how the size of LNPs—the core vehicles for mRNA vaccines and gene therapies—affects cellular delivery efficiency and gene expression.

This study is significant because it experimentally proved that the "size itself" of the lipid nanoparticle, rather than just its chemical components, is a key factor governing delivery efficiency. It is being recognized for providing specific design criteria to enhance the performance of mRNA vaccines and next-generation gene therapy technologies.

The "Delivery Box" for Genetic Blueprints

mRNA vaccines and gene therapies do not deliver medicinal substances directly; instead, they deliver blueprints (mRNA) for making proteins into cells. Since mRNA is highly unstable and struggles to enter cells on its own, LNPs act as tiny, droplet-shaped "delivery boxes" that encapsulate and protect the mRNA.

The research team conducted experiments by creating LNPs of different sizes while using the same lipid components and the same mRNA. To achieve this, they utilized microfluidic technology, which precisely controls minute fluid flows at the nanometer scale—thousands of times thinner than a human hair.

The Result: Smaller is Better, Up to a Point

The study found that smaller particles enter cells more effectively and increase protein production. Analysis suggested that smaller particles require less energy to penetrate the cell membrane. Essentially, "smaller boxes" are easier for cells to accept.

Interestingly, the study also revealed that LNPs are not necessarily better just because they are smaller. The team discovered that excessively small LNPs can become structurally unstable in the body’s environment. As the protective substance (PEG) on the particle surface detaches, delivery efficiency actually decreases. This suggests that finding the "optimal size" is crucial in the development of mRNA therapeutics.

New Possibilities for Mass Production

In addition to experimental results, the team used Computational Fluid Dynamics (CFD) simulations to analyze the physical principles behind LNP formation. The results suggested that LNP size is determined not by complex turbulence (violent swirling) but by diffusion-dominated mixing—the speed at which molecules move across boundaries, similar to how a drop of ink spreads in water.

This finding opens the possibility of precisely controlling LNP size using simpler systems without the need for complex equipment, providing essential data for the mass production and process standardization of mRNA treatments.

Professor Koo Hee-beom stated, "This research intuitively demonstrates the importance of particle size as a core factor in determining the performance of mRNA vehicles. It will serve as a practical standard for designing safer and more efficient delivery systems in the development of mRNA vaccines and gene therapies targeting various diseases."

This research was supported by the Catholic Medical Center Basic Medicine Research Group, the Mid-career Researcher Program, the Gene Editing/Control/Restoration Technology Development Project, and the Post-Doc Growth Collaborative Research Project. The findings were published in the international journal 《Journal of Nanobiotechnology》 (IF 12.6), a leading publication in the field of nanobiotechnology.

△ Figure Description: Schematic diagram of mRNA delivery effectiveness according to lipid nanoparticle size.