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Successful batch and continuous lyophilization of mRNA LNP formulations depend on cryoprotectants and ionizable lipids

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What this work says

Outgoing claims: the papers this work cites, builds on, or argues with.

inferredcites →https://doi.org/10.1002/ange.202008319openalex-snapshot
Current Status of COVID‐19 (Pre)Clinical Vaccine Development
inferredcites →https://doi.org/10.1016/j.addr.2021.114000openalex-snapshot
Messenger RNA-based vaccines: Past, present, and future directions in the context of the COVID-19 pandemic
inferredcites →https://doi.org/10.1016/j.bioactmat.2020.03.001openalex-snapshot
Long-term storage of lipid-like nanoparticles for mRNA delivery
inferredcites →https://doi.org/10.1016/j.ejpb.2017.01.001openalex-snapshot
Mechanistic modelling of infrared mediated energy transfer during the primary drying step of a continuous freeze-drying process
inferredcites →https://doi.org/10.1016/j.ejpb.2019.06.027openalex-snapshot
Achieving continuous manufacturing in lyophilization: Technologies and approaches
inferredcites →https://doi.org/10.1016/j.ejpb.2020.09.009openalex-snapshot
A primary drying model-based comparison of conventional batch freeze-drying to continuous spin-freeze-drying for unit doses
inferredcites →https://doi.org/10.1016/j.ijpharm.2015.05.025openalex-snapshot
Evaluation of spin freezing versus conventional freezing as part of a continuous pharmaceutical freeze-drying concept for unit doses
inferredcites →https://doi.org/10.1016/j.ijpharm.2021.120586openalex-snapshot
mRNA-lipid nanoparticle COVID-19 vaccines: Structure and stability
inferredcites →https://doi.org/10.1016/j.xphs.2020.12.006openalex-snapshot
Addressing the Cold Reality of mRNA Vaccine Stability
inferredcites →https://doi.org/10.1021/acs.molpharmaceut.8b01290openalex-snapshot
Lipid Nanoparticles for Delivery of Therapeutic RNA Oligonucleotides
inferredcites →https://doi.org/10.1023/b:pham.0000016234.73023.75openalex-snapshot
Design of Freeze-Drying Processes for Pharmaceuticals: Practical Advice
inferredcites →https://doi.org/10.1038/s41578-021-00358-0openalex-snapshot
Lipid nanoparticles for mRNA delivery
inferredcites →https://doi.org/10.3109/03639045.2011.645835openalex-snapshot
Optimization of the lyophilization process for long-term stability of solid–lipid nanoparticles
inferredcites →https://doi.org/10.3389/fchem.2018.00004openalex-snapshot
Detection of Collapse and Crystallization of Saccharide, Protein, and Mannitol Formulations by Optical Fibers in Lyophilization
inferredcites →https://doi.org/10.3390/pharmaceutics10030131openalex-snapshot
Drying Technologies for the Stability and Bioavailability of Biopharmaceuticals
inferredcites →https://doi.org/10.3390/pharmaceutics13122126openalex-snapshot
Spin Freezing and Its Impact on Pore Size, Tortuosity and Solid State
inferredcites →https://doi.org/10.3390/vaccines10030349openalex-snapshot
COVID-19 Vaccine: Between Myth and Truth
inferredcites →https://doi.org/10.3390/vaccines9010065openalex-snapshot
Nanomaterial Delivery Systems for mRNA Vaccines
inferredcites →https://doi.org/10.3390/vaccines9091033openalex-snapshot
Challenges of Storage and Stability of mRNA-Based COVID-19 Vaccines

What points at this work

Incoming claims: where this work appears in other papers’ reference lists and arguments.

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inferred← citeshttps://doi.org/10.1002/adhm.202501788openalex-snapshot
Admixing of mRNA with Pre‐Formed Lipid Nanoparticles Containing a Slightly‐Cationic Ionizable Lipid Allows for Efficient mRNA Transfection In Vitro and In Vivo
inferred← citeshttps://doi.org/10.1002/advs.202508506openalex-snapshot
Hyperspectral Imaging Techniques for Lyophilization: Advances in Data‐Driven Modeling Strategies and Applications
inferred← citeshttps://doi.org/10.1002/btpr.3378openalex-snapshot
Current challenges and recent advances on the path towards continuous biomanufacturing
inferred← citeshttps://doi.org/10.1002/mba2.70036openalex-snapshot
Investigations Into the Influence of Ionizable Lipids on the Stability of Lipid Nanoparticle
inferred← citeshttps://doi.org/10.1002/smll.202306892openalex-snapshot
Lipid Nanoparticle Encapsulation Empowers Poly(I:C) to Activate Cytoplasmic RLRs and Thereby Increases Its Adjuvanticity
inferred← citeshttps://doi.org/10.1007/978-1-0716-5416-3_5openalex-snapshot
Emerging Manufacturing Technologies in Freeze-Drying of Pharmaceuticals
inferred← citeshttps://doi.org/10.1007/s00203-025-04596-6openalex-snapshot
Lipid nanoparticle–based mRNA platforms for mucosal HIV vaccines: formulation advances, immune mechanisms, and translational pathways
inferred← citeshttps://doi.org/10.1007/s11095-026-04039-xopenalex-snapshot
Freezing-Induced Stress in mRNA-Lipid Nanoparticles During Lyophilization: Mechanistic Insights From Process and Formulation Studies
inferred← citeshttps://doi.org/10.1016/j.addr.2024.115419openalex-snapshot
Advances in the design and delivery of RNA vaccines for infectious diseases
inferred← citeshttps://doi.org/10.1016/j.addr.2026.115934openalex-snapshot
Redox-responsive LNPs for therapeutics delivery
inferred← citeshttps://doi.org/10.1016/j.bbcan.2025.189515openalex-snapshot
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inferred← citeshttps://doi.org/10.1016/j.biomaterials.2024.122897openalex-snapshot
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inferred← citeshttps://doi.org/10.1016/j.biopha.2023.115361openalex-snapshot
mRNA vaccine in gastrointestinal tumors: Immunomodulatory effects and immunotherapy
inferred← citeshttps://doi.org/10.1016/j.biopha.2024.117108openalex-snapshot
Advances in the development of lipid nanoparticles for ophthalmic therapeutics
inferred← citeshttps://doi.org/10.1016/j.cherd.2025.01.003openalex-snapshot
Continuous manufacturing based paradigm shift in pharmaceuticals production and current regulatory framework
inferred← citeshttps://doi.org/10.1016/j.ejpb.2026.115065openalex-snapshot
Cryomilling of freeze dried low-Tg sugar glasses: A versatile method to prepare inhalable dry powder formulations
inferred← citeshttps://doi.org/10.1016/j.ijpharm.2023.123688openalex-snapshot
Effect of lipid composition on RNA-Lipid nanoparticle properties and their sensitivity to thin-film freezing and drying
inferred← citeshttps://doi.org/10.1016/j.ijpharm.2024.124696openalex-snapshot
Cryoprotectant optimization for enhanced stability and transfection efficiency of pDNA-loaded ionizable lipid nanoparticles
inferred← citeshttps://doi.org/10.1016/j.ijpharm.2025.126301openalex-snapshot
End-to-end digital twin software for continuous mRNA manufacturing
inferred← citeshttps://doi.org/10.1016/j.ijpharm.2025.126426openalex-snapshot
Recent advances in freeze-drying technologies for mRNA vaccines against infectious diseases
inferred← citeshttps://doi.org/10.1016/j.ijpharm.2026.127032openalex-snapshot
Quality-by-Design (QbD) optimization of lyophilization parameters for siRNA-loaded LNPs using sequential Design of Experiments (DoE)
inferred← citeshttps://doi.org/10.1016/j.iphar.2026.100006openalex-snapshot
Nanotechnology-based self-amplifying RNA
inferred← citeshttps://doi.org/10.1016/j.jconrel.2024.07.052openalex-snapshot
Physicochemical and structural insights into lyophilized mRNA-LNP from lyoprotectant and buffer screenings
inferred← citeshttps://doi.org/10.1016/j.jconrel.2024.09.030openalex-snapshot
Thin-film freeze-drying of an influenza virus hemagglutinin mRNA vaccine in unilamellar lipid nanoparticles with blebs
inferred← citeshttps://doi.org/10.1016/j.jconrel.2025.113944openalex-snapshot
Lyophilized SARS-CoV-2 self-amplifying RNA vaccines for microneedle array patch delivery
inferred← citeshttps://doi.org/10.1016/j.jconrel.2025.114259openalex-snapshot
Overcoming cold chain challenges: Cryoprotection of self-amplifying mRNA polyplexes for long-term storage at ambient temperature
inferred← citeshttps://doi.org/10.1016/j.jconrel.2026.114749openalex-snapshot
A functional lyoprotectant platform enables storage-stable, mucus-penetrating siRNA delivery to the lung
inferred← citeshttps://doi.org/10.1016/j.jconrel.2026.114783openalex-snapshot
Oscillation-generating micromixing (FDmiX) – a new method for manufacturing of mRNA-lipid nanoparticles with scalable high-throughput production
inferred← citeshttps://doi.org/10.1016/j.jconrel.2026.114888openalex-snapshot
Advances in stabilizing lipid-based nanoparticles: The central role of lyophilization
inferred← citeshttps://doi.org/10.1016/j.jconrel.2026.115148openalex-snapshot
Loss of internal structural order induced by freezing and lyophilization correlates with reduced in vitro activity of mRNA lipid nanoparticles
inferred← citeshttps://doi.org/10.1016/j.jconrel.2026.115189openalex-snapshot
The hidden half of lipid nanoparticle manufacturing: Downstream processing
inferred← citeshttps://doi.org/10.1016/j.jddst.2025.107909openalex-snapshot
Spin freeze-drying in continuous biomanufacturing: Boon or mirage?
inferred← citeshttps://doi.org/10.1016/j.jddst.2026.108746openalex-snapshot
Development of a multifunctional DMSO-containing buffer to optimize mRNA-LNP intracellular delivery, cryostability, and vaccine efficacy
inferred← citeshttps://doi.org/10.1016/j.jpha.2024.100996openalex-snapshot
Machine learning-driven optimization of mRNA-lipid nanoparticle vaccine quality with XGBoost/Bayesian method and ensemble model approaches
inferred← citeshttps://doi.org/10.1016/j.lanepe.2026.101659openalex-snapshot
Oncolytic viruses and neoantigen vaccines: opportunities and challenges in priming antitumour immunity
inferred← citeshttps://doi.org/10.1016/j.mtbio.2026.103568openalex-snapshot
Overcoming hepatic tropism: Precision engineering of lipid nanoparticles for extrahepatic RNA delivery
inferred← citeshttps://doi.org/10.1016/j.nxmate.2026.102375openalex-snapshot
Engineering mRNA-LNP therapeutics: Nanomaterials for preservation, controlled release, and inhalation delivery
inferred← citeshttps://doi.org/10.1016/j.seppur.2025.134837openalex-snapshot
Continuous purification of mRNA by precipitation and sequential TFF
inferred← citeshttps://doi.org/10.1016/j.xphs.2024.12.013openalex-snapshot
Recent advances in drying and development of solid formulations for stable mRNA and siRNA lipid nanoparticles
inferred← citeshttps://doi.org/10.1021/acs.molpharmaceut.4c00826openalex-snapshot
Development of Thermally Stable mRNA-LNP Delivery Systems: Current Progress and Future Prospects
inferred← citeshttps://doi.org/10.1021/acsnano.4c10154openalex-snapshot
Tetrahydropyrimidine Ionizable Lipids for Efficient mRNA Delivery
inferred← citeshttps://doi.org/10.1021/acsnano.4c14041openalex-snapshot
Targeted Delivery of mRNA with Polymer–Lipid Nanoparticles for In Vivo Base Editing
inferred← citeshttps://doi.org/10.1021/jacs.4c15688openalex-snapshot
Galloyl Dialkyl Lipids Drive Encapsulation of Peptides into Lipid Nanoparticles by Hydrogen Bonding
inferred← citeshttps://doi.org/10.1038/s41467-024-54877-9openalex-snapshot
Intratumoral delivery of lipid nanoparticle-formulated mRNA encoding IL-21, IL-7, and 4-1BBL induces systemic anti-tumor immunity
inferred← citeshttps://doi.org/10.1038/s41587-026-03331-wopenalex-snapshot
Accelerated discovery of thermostable mRNA–lipid nanoparticle vaccines using data-efficient AI
inferred← citeshttps://doi.org/10.1038/s44222-026-00424-8openalex-snapshot
Expanding global access to mRNA vaccines
inferred← citeshttps://doi.org/10.1039/d5nr05189dopenalex-snapshot
Engineered strategies for enhancing mRNA vaccine stability in delivery and storage
inferred← citeshttps://doi.org/10.1042/ebc20253009openalex-snapshot
Advancing mRNA vaccines for infectious diseases: key components, innovations, and clinical progress
inferred← citeshttps://doi.org/10.1080/13880209.2025.2498169openalex-snapshot
Delivery of small interfering RNA through lyophilized natural lipid nanoparticles: effects of natural lipid selection
inferred← citeshttps://doi.org/10.1080/14760584.2025.2596674openalex-snapshot
Not so cold! Improving the thermostability of mRNA vaccines
inferred← citeshttps://doi.org/10.1080/17435889.2025.2555507openalex-snapshot
Emerging lipid nanoparticle systems capable of efficient intramuscular RNA delivery
inferred← citeshttps://doi.org/10.1080/21645515.2024.2342592openalex-snapshot
Long-term stability and immunogenicity of lipid nanoparticle COVID-19 mRNA vaccine is affected by particle size
inferred← citeshttps://doi.org/10.1080/21645515.2025.2477384openalex-snapshot
Lyophilized monkeypox mRNA lipid nanoparticle vaccines with long-term stability and robust immune responses in mice
inferred← citeshttps://doi.org/10.1080/21645515.2025.2597629openalex-snapshot
mRNA vaccine platforms and novel delivery systems: From mechanistic principles to clinical translation
inferred← citeshttps://doi.org/10.1186/s11671-026-04864-4openalex-snapshot
Critical chemistry manufacturing and controls considerations for mRNA lipid nanoparticle translation
inferred← citeshttps://doi.org/10.1186/s41120-026-00146-6openalex-snapshot
Drying technologies for messenger RNA and other nucleic acid-lipid nanoparticles: advances in freeze-drying and beyond
inferred← citeshttps://doi.org/10.1186/s41120-026-00147-5openalex-snapshot
Lyophilized monoclonal antibody (mAb) encoded mRNA—lipid nanoparticles (LNPs) lead to stable in vivo expression of mAb after room temperature storage
inferred← citeshttps://doi.org/10.1186/s43556-026-00600-7openalex-snapshot
mRNA lipid nanoparticle vaccines: current status, challenges and future prospects
inferred← citeshttps://doi.org/10.21203/rs.3.rs-4000095/v1openalex-snapshot
Capsule coffee-inspired customizable production of nucleic acid medicine using a rapid on-site microfluidic assembly (ROMA) technology
inferred← citeshttps://doi.org/10.21203/rs.3.rs-5047616/v1openalex-snapshot
Tackling intrinsic instability of mRNA vaccine by a rapid onsite microfluidic assembly (ROMA) technology
inferred← citeshttps://doi.org/10.3389/fimmu.2026.1873905openalex-snapshot
In vivo immune engineering via mRNA therapeutics: reprogramming the post-infarction cardiac microenvironment
inferred← citeshttps://doi.org/10.3390/biom13101497openalex-snapshot
Enabling mRNA Therapeutics: Current Landscape and Challenges in Manufacturing
inferred← citeshttps://doi.org/10.3390/biom15030359openalex-snapshot
Revolutionizing mRNA Vaccines Through Innovative Formulation and Delivery Strategies
inferred← citeshttps://doi.org/10.3390/ijms241914679openalex-snapshot
Cancer/Testis Antigens as Targets for RNA-Based Anticancer Therapy
inferred← citeshttps://doi.org/10.3390/ijms262010015openalex-snapshot
Unraveling Lyophilization and Redispersion Effects on Miktoarm Polymer-Based Nanoformulations
inferred← citeshttps://doi.org/10.3390/pharmaceutics15071819openalex-snapshot
Development of an Alcohol Dilution–Lyophilization Method for the Preparation of mRNA-LNPs with Improved Storage Stability
inferred← citeshttps://doi.org/10.3390/pharmaceutics16111366openalex-snapshot
The Impact of COVID-19 on RNA Therapeutics: A Surge in Lipid Nanoparticles and Alternative Delivery Systems
inferred← citeshttps://doi.org/10.3390/pharmaceutics17050550openalex-snapshot
A Review on the Stability Challenges of Advanced Biologic Therapeutics
inferred← citeshttps://doi.org/10.3390/pharmaceutics18010121openalex-snapshot
Freeze-Drying in Sucrose Followed by Cryomilling Enables the Formulation of sa-mRNA–LNP Powders for Inhalation
inferred← citeshttps://doi.org/10.3390/vaccines12020186openalex-snapshot
Lipid Nanoparticle (LNP) Delivery Carrier-Assisted Targeted Controlled Release mRNA Vaccines in Tumor Immunity
inferred← citeshttps://doi.org/10.3390/vaccines13080853openalex-snapshot
Freeze-Drying of mRNA-LNPs Vaccines: A Review
inferred← citeshttps://doi.org/10.53941/rmd.2024.100003openalex-snapshot
Application of Saccharide Cryoprotectants in the Freezing or Lyophilization Process of Lipid Nanoparticles Encapsulating Gene Drugs for Regenerative Medicine
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