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Storage Buffers Boost mRNA Vaccine and LNP Efficiency

Researchers at The University of Texas at Austin and Eli Lilly and Company have identified how storage buffer solutions alter the internal structure and delivery efficiency of mRNA lipid nanoparticles. Published in ACS Nano, the study demonstrates that…

Storage Buffers Boost mRNA Vaccine and LNP Efficiency

Researchers at The University of Texas at Austin and Eli Lilly and Company have identified how storage buffer solutions alter the internal structure and delivery efficiency of mRNA lipid nanoparticles. Published in ACS Nano, the study demonstrates that selecting appropriate storage solutions can preserve the stability and potency of mRNA-based treatments after freezing and shipping.

Storage Buffer Composition and Freeze-Thaw Stability

Lipid nanoparticles serve as the delivery vehicles for mRNA vaccines and gene-editing therapies, carrying fragile genetic instructions into human cells. These nanoparticles must often be frozen for global distribution, but temperature fluctuations and freezing cycles can degrade their physical characteristics. According to the research published in ACS Nano by Meysam Mohammadi-Zerankeshi and colleagues, variations in storage buffers directly impact nanoparticle size, uniformity, and cargo encapsulation.

The research team tested three distinct storage buffers: Tris, histidine, and citrate. Experiments revealed that citrate buffer improved delivery efficiency when samples were stored in the refrigerator, but failed to protect the nanoparticles during freezing. In contrast, Tris buffer preserved stability, maintained the desired internal structure, and improved potency following freeze-thaw cycles.

Manufacturing Optimization and Dosage Efficiency

Current mRNA delivery systems face significant efficiency hurdles. Approximately 5% to 10% of mRNA is properly delivered to the target. To compensate for this low delivery rate, treatments often require higher doses, which can intensify post-vaccination side effects such as feeling rough for a day or two.

“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. By refining storage buffers and enhancing nanoparticle stability, manufacturers can potentially achieve equal therapeutic effects using lower doses, thereby reducing side effects for patients.

Collaborative Scale-Up and Future Drug Design

The project builds on a multi-year partnership between UT Austin researchers—including Chemical Engineering Professor Keith Johnston—and pharmaceutical leader Eli Lilly and Company. This industry collaboration provided academic researchers access to advanced synthesis tools and pharmaceutically relevant samples, allowing them to scale up nanoparticle production and test formulations across four human cell lines.

Gaining a precise, mechanistic understanding of RNA-lipid interactions enables Lilly to design more effective therapeutics. The findings from the UT Austin and Eli Lilly study offer a concrete pathway for improving the global supply chain, storage resilience, and clinical effectiveness of future mRNA vaccines and gene therapies.

Storage & Logistics of mRNA Vaccines
About the author: Dr Natalie Singh - Health Editor

Board‑certified internal‑medicine physician and MPH. Natalie authored peer‑reviewed studies on infectious disease and served as medical editor. “Dr. Natalie Singh delivers evidence‑based health news, medical breakthroughs, and expert wellness guidance.”