91视频 College of Pharmacy (UHCOP) Pharmacological and Pharmaceutical Sciences (PPS) Ph.D. student Urmila Kafle has earned two national honors for research that could change how scientists think about designing more effective mRNA delivery systems.
Kafle was selected to receive an AAPS Best Poster Award, one of only three presented annually by the organization, for the poster 鈥淚onizable Lipid Composition Reveals Post-Endosomal mRNA Dissociation as a Key Barrier in LNP Delivery.鈥� She will present the work at the 2026 AAPS PharmSci 360 meeting Oct. 25-28 in New Orleans. The same research was also selected for a 2026 AAPS Best Abstract Award.
The award-winning research was conducted in the laboratory of Presidential Frontier Faculty member and Assistant Professor Fanfei Meng, Ph.D., and led by former postdoctoral fellow Hoang Quan Truong, Ph.D., who played a central role in developing, executing and interpreting the study. Kafle contributed to the research as part of the team and prepared and presented the work recognized by AAPS.
The research examines a frequently overlooked challenge in mRNA delivery that could influence how scientists develop future vaccines and therapeutics.
鈥淚鈥檓 honored to receive this recognition from AAPS,鈥� Kafle said. 鈥淭his project has given me the opportunity to better understand the challenges involved in mRNA delivery and to contribute to research that could help improve future mRNA-based medicines. I鈥檓 very grateful to Dr. Meng, Dr. Truong and our entire research team for their mentorship, guidance and support.鈥�
The AAPS recognition follows Kafle鈥檚 first-place finish in the Graduate Oral Presentation category at the 2026 PPS Research Symposium.
Understanding the Challenge of mRNA Delivery
Many mRNA medicines rely on tiny fat-based particles called lipid nanoparticles, or LNPs, to protect mRNA and carry it into cells. This technology gained widespread attention through its use in mRNA vaccines, such as the Moderna COVID-19 vaccine, and is now being explored for a growing range of medical applications.
One of the biggest challenges in mRNA delivery occurs after an LNP enters a cell. The particle initially becomes trapped inside a small membrane-bound compartment called an endosome. For years, researchers have devoted considerable attention to helping LNPs escape from these compartments so their mRNA cargo can reach the main interior of the cell.
But the research team found that escaping the endosome may be only part of the challenge.
Even after reaching the right place inside the cell, mRNA can remain too tightly associated with the lipids that carried it there. If the carrier does not efficiently release the mRNA, the cell may not be able to fully access its instructions and produce the desired protein.
In simple terms, delivering a package to the correct address is not enough. The package also has to be opened.
Optimizing Lipid Composition
To understand this process, the research team changed the amount of a key LNP ingredient known as an ionizable lipid.
Ionizable lipids play several important roles: They help package and protect mRNA and assist with its delivery into cells. But they also interact directly with mRNA, raising an important question: Could an interaction that is beneficial during delivery become a disadvantage once the mRNA reaches its destination?
The researchers found that more ionizable lipid was not necessarily better.
LNPs containing approximately 30% ionizable lipid produced substantially more protein than formulations containing the higher levels typically used in clinically relevant LNP formulations. However, reducing the amount further to 20% caused performance to decline.
The findings suggest that optimizing ionizable lipid content, rather than simply increasing it, could improve the effectiveness of mRNA delivery systems.
Identifying a Hidden Delivery Barrier
The researchers then asked why the optimized formulation produced more protein.
Surprisingly, the different formulations entered cells at similar levels and were also comparable in their ability to escape from endosomes. These findings suggested that the major difference occurred after endosomal escape.
The optimized formulation allowed mRNA to separate more readily from its lipid carrier inside the cell, making the mRNA more accessible for protein production.
鈥淢uch of the mRNA delivery field has focused on helping lipid nanoparticles escape from endosomes, but our findings show that getting out is not the whole story,鈥� said Meng. 鈥淭he nanoparticle also must let go of the mRNA so the cell can use it. This gives us another important factor to consider when designing more effective mRNA delivery systems.鈥�
The researchers confirmed the importance of their findings in murine models. The optimized formulation produced greater protein expression following both intramuscular and intravenous administration. When the team tested LNPs carrying mRNA encoding an antigen, the optimized formulation also generated stronger antibody and cellular immune responses.
Implications for Future mRNA Medicines
The findings offer a new consideration for developing more effective mRNA-based medicines, demonstrating how adjustments to lipid nanoparticle composition could improve delivery and potentially strengthen the performance of future vaccines and therapeutics.
鈥淯rmila made important contributions and did an excellent job presenting the work,鈥� Meng added. 鈥淚 am very pleased to see Urmila鈥檚 presentation and the significance of our team鈥檚 research recognized by AAPS.