Optimizing Storage Buffers to Improve mRNA-LNP Vaccine Stability and Efficiency
- Researchers at The University of Texas at Austin have partnered with pharmaceutical leader Eli Lilly and Company to examine how storage buffer solutions alter the internal structure and...
- The investigation centers on lipid nanoparticles, which serve as the primary delivery system for genetic instructions in COVID-19 vaccines and emerging gene-editing treatments.
- According to the findings, the choice of storage buffer directly shapes the internal nanostructure of the particle.
Researchers at The University of Texas at Austin have partnered with pharmaceutical leader Eli Lilly and Company to examine how storage buffer solutions alter the internal structure and delivery efficiency of mRNA lipid nanoparticles. Published in ACS Nano, the joint study details how different storage environments affect the stability of these microscopic delivery vehicles during freezing and global distribution.
The Hidden Vulnerability in mRNA Delivery
The investigation centers on lipid nanoparticles, which serve as the primary delivery system for genetic instructions in COVID-19 vaccines and emerging gene-editing treatments. These particles encapsulate therapeutic mRNA and transport it safely into human cells. However, maintaining stability while freezing and shipping these medicines remains a persistent hurdle for drug manufacturers.
Inside the Nanoparticle Storage Dilemma
According to the findings, the choice of storage buffer directly shapes the internal nanostructure of the particle. This structural configuration dictates how efficiently the cargo is released once inside the body.
“Our study shows that something as simple as the storage solution can make a huge difference in how well mRNA medicines work,” said Alex Marras, an assistant professor in the Cockrell School of Engineering’s Walker Department of Mechanical Engineering at UT Austin.
Testing Tris, Histidine, and Citrate Buffers
To evaluate performance, the research team tested specific buffer solutions including Tris, histidine, and citrate. Each buffer impacted the nanoparticles differently regarding freeze-thaw survival and cellular delivery. Citrate buffer improved delivery efficiency when stored under standard refrigeration, but failed to protect the particles during freezing processes.
Conversely, the Tris buffer preserved particle stability, maintained the desired internal structure, and retained high potency after undergoing freezing and thawing cycles.
“These lipid nanoparticles protect mRNA and help deliver it into cells, but the nanoparticles themselves are also sensitive to their storage environment,” said Meysam Mohammadi-Zerankeshi, a Ph.D. student in Marras’ laboratory and the first author of the study. If nanoparticles aggregate or lose their cargo during temperature shifts, delivery efficiency drops and treatments lose effectiveness.
Industry Partnership Fuels Advanced Testing
The multi-year collaboration between UT Austin and Eli Lilly—which has also included prior work on antibodies and siRNA alongside UT Austin Chemical Engineering Professor Keith Johnston—provided the academic team with advanced tools and pharmaceutically relevant samples. This partnership enabled researchers to scale up nanoparticle synthesis and test formulations across four distinct human cell lines.
Pathways Toward Lower Doses and Fewer Side Effects
Industry partners can use these mechanistic insights regarding RNA-lipid interactions to refine future therapeutic designs. Because standard mRNA delivery currently routes only 5 to 10 percent of active material to target cells, optimizing storage buffers and structural stability offers a pathway toward higher efficiency. Improved delivery could eventually allow manufacturers to achieve equivalent therapeutic outcomes using lower doses, potentially minimizing side effects for patients.