ArticleJournal of controlled release : official journal of the Controlled Release Society2023
Continuous freeze-drying of messenger RNA lipid nanoparticles enables storage at higher temperatures.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 121 citations in OpenAlex.
- Overcoming hepatic tropism: Precision engineering of lipid nanoparticles for extrahepatic RNA delivery.Materials today. Bio · 2026Review
- Improving the Quality of Lyophilized Animal Vaccines: A Review of Optimization Strategies for Freeze-Drying Processes.Veterinary sciences · 2026Review
- Spray Freeze Drying for Solid Formulations of RNA Lipid Nanoparticles.AAPS PharmSciTech · 2026Article
- An Investigation of Water Vapor Sorption for Improving Reconstitution Pathways of Freeze-Dried Lipid Nanoparticles Stabilized by Trehalose/Mannitol Excipients.AAPS PharmSciTech · 2026Article
- Advancements of mRNA-lipid nanoparticle links to gene editing and immune responses.Journal, genetic engineering & biotechnology · 2026Review
- Lipid Nanoparticles for Gene Therapy: Unresolved Challenges in Manufacturing, Transdermal Delivery, Machine Learning, Endosomal Escape, and the Protein Corona.Pharmaceutics · 2026Review
- Bacterial mRNA Vaccines: Programming Immunity Against Antimicrobial Resistance.Drug development research · 2026Review
- Two Classes of Protein Therapeutics: Why Dose-Response Architecture Defines the Boundary of mRNA Medicines.Pharmaceutics · 2026Review
- Advances in improving cancer immunotherapy with nanotechnology: from smart nanoparticles to synergistic combination strategies.Molecular cancer · 2026Review
- Next-Generation Nanocarrier Platforms for RNA Vaccines: Advances in Formulation, Stability Engineering, and Translational Manufacturing Challenges.Pharmaceutics · 2026Review
- Post-loading ribonucleic acid into lipid nanoparticle carriers.bioRxiv : the preprint server for biology · 2026Article
- From Morphology to Mechanism: Cryo-Electron Microscopy Insights into Lipid Nanoparticles for RNA Delivery.ACS nano · 2026Review
- Analytical Ultracentrifugation in Different High-Density Media Allows to Assess Heterogeneity of mRNA-Lipid Nanoparticles.Small methods · 2026Article
- Development of a microneedle patch for delivery of mRNA-lipid nanoparticles.Drug delivery and translational research · 2026Article
- Storage Buffer Composition Impacts Internal Structure, Freeze-Thaw Stability, and Transfection Efficiency of mRNA-Lipid Nanoparticles.ACS nano · 2026Article
- Strategic lipid nanoparticle design dictates retinal delivery post inner limiting membrane disruption.Drug delivery and translational research · 2026Article
- Recent advances in the application of polymeric nanoparticles to the pulmonary delivery of mRNA.Nanomedicine (London, England) · 2026Review
- A Cryoprotectant-Compatible Nanoporous Platform for Stable and Scalable Delivery of Biopharmaceuticals.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- mRNA Lipid Nanoparticles for Cell Engineering in Vivo and in Vitro: Current Applications and Future Directions.MedComm · 2026Review
- Effects of Different Drying Methods on the Quality ofFoods (Basel, Switzerland) · 2026Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Messenger RNA (mRNA) lipid nanoparticles (LNPs) have emerged at the forefront during the COVID-19 vaccination campaign. Despite their tremendous success, mRNA vaccines currently require storage at deep freeze temperatures which complicates their storage and distribution, and ultimately leads to lower accessibility to low- and middle-income countries. To elaborate on this challenge, we investigated freeze-drying as a method to enable storage of mRNA LNPs at room- and even higher temperatures. More specifically, we explored a novel continuous freeze-drying technique based on spin-freezing, which has several advantages compared to classical batch freeze-drying including a much shorter drying time and improved process and product quality controlling. Here, we give insight into the variables that play a role during freeze-drying by evaluating the impact of the buffer and mRNA LNP formulation (ionizable lipid to mRNA weight ratio) on properties such as size, morphology and mRNA encapsulation. We found that a sufficiently high ionizable lipid to mRNA weight ratio was necessary to prevent leakage of mRNA during freeze-drying and that phosphate and Tris, but not PBS, were appropriate buffers for lyophilization of mRNA LNPs. We also studied the stability of optimally lyophilized mRNA LNPs at 4 °C, 22 °C, and 37 °C and found that transfection properties of lyophilized mRNA LNPs were maintained during at least 12 weeks. To our knowledge, this is the first study that demonstrates that optimally lyophilized mRNA LNPs can be safely stored at higher temperatures for months without losing their transfection properties.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.