This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Researchers at The University of Texas at Austin have teamed up with pharmaceutical company Eli Lilly and Company to uncover how storage conditions affect mRNA lipid nanoparticles (LNPs), the technology behind COVID-19 vaccines and other treatments, and how to make them more effective. The study, which also includes researchers from Boston University, examines how storage and distribution conditions, often involving freezing, affect how well mRNA-LNP therapeutics work by the time they reach patients.
Choosing the right "storage buffers" can shape the nanoparticles' internal structure, which governs how efficiently mRNA is delivered into cells and turned into protein. That step helps determine the treatment's effectiveness, whether it is a vaccine or a gene-editing therapy. "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 and one of the lead researchers on the study published in ACS Nano.
"By understanding how the buffer molecules influence particle nanostructure and their interactions with cellular compartments, we can help make these therapies more stable and effective, even after they've been frozen and shipped around the world." Tiny mRNA carriers called lipid nanoparticles deliver genetic instructions into cells, prompting them to make proteins that treat or prevent disease. This system, the researchers say, is the gold standard for delivering therapeutic RNA, but it still faces challenges. Buffer solutions are used to keep the nanoparticles stable during freezing and shipping.
That has proved challenging because the nanoparticles can be sensitive to changes in size, uniformity and how well they encapsulate their therapeutic mRNA cargo. The research team investigated how different storage buffers—specifically Tris, histidine and citrate—affect the internal structure, stability and delivery efficiency of mRNA-LNPs. Their experiments revealed that the type and concentration of buffer influence not only how well the nanoparticles survive freezing and thawing but also the structural changes they undergo during delivery.
Those changes control how effectively they deliver mRNA into cells. Citrate buffer helped the nanoparticles deliver mRNA more efficiently when refrigerated but could not protect them during freezing. Tris buffer improved potency after freezing and thawing, preserving stability, the desired internal structure and mRNA delivery.
"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 doctoral student in Marras' lab and the paper's first author. "If they become unstable during freezing and thawing, they can aggregate or lose their cargo, reducing delivery efficiency, and then the treatments don't work." Marras' collaborations with Lilly date back several years and include work with UT Austin chemical engineering professor Keith Johnston, as well as other projects focused on antibodies and siRNA. The collaborations gave the researchers access to additional tools and samples relevant to pharmaceutical development, allowing them to scale up nanoparticle synthesis and test the particles across four human cell lines.
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