Continuous freeze-drying of messenger RNA lipid nanoparticles enables storage at higher temperatures

Meulewaeter, Sofie; Nuytten, Gust; Cheng, Miffy H. Y.; Smedt, Stefaan C. De; Cullis, Pieter R.; Beer, Thomas De; Lentacker, Ine; Verbeke, R

doi:10.1016/j.jconrel.2023.03.039

Cited by 53 publications

(13 citation statements)

References 51 publications

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“…They found that mRNA nanoparticles were stable at 4 °C, 22 °C, and 37 °C, and that the transfection properties of lyophilized particles were maintained during at least 12 weeks. [ 213 ] An exciting possibility is that improved process controls such as this would enable the reconstitution of the vaccine wherever it is to be delivered within the world, then delivered through a hollow MNA directly to immune cell‐rich dermal layers.…”

Section: Strategies To Improve the Stability Of Immunotherapies And V...mentioning

confidence: 99%

Exploiting Unique Features of Microneedles to Modulate Immunity

et al. 2023

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Microneedle arrays (MNAs) are small patches containing hundreds of short projections that deliver signals directly to dermal layers without causing pain. These technologies are of special interest for immunotherapy and vaccine delivery because they directly target immune cells concentrated in the skin. The targeting abilities of MNAs result in efficient immune responses—often more protective or therapeutic—compared to conventional needle delivery. MNAs also offer logistical benefits, such as self‐administration and transportation without refrigeration. Thus, numerous preclinical and clinical studies are exploring these technologies. Here we discuss the unique advantages of MNA, as well as critical challenges – such as manufacturing and sterility issues – the field faces to enable widespread deployment. We explain how MNA design parameters can be exploited for controlled release of vaccines and immunotherapies, and the application to preclinical models of infection, cancer, autoimmunity, and allergies. We also discuss specific strategies to reduce off‐target effects compared to conventional vaccine delivery routes, and novel chemical and manufacturing controls that enable cargo stability in MNAs across flexible intervals and temperatures. We then examine clinical research using MNAs. We conclude with drawbacks of MNAs and the implications, and emerging opportunities to exploit MNAs for immune engineering and clinical use.This article is protected by copyright. All rights reserved

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Section: Strategies To Improve the Stability Of Immunotherapies And V...mentioning

confidence: 99%

Exploiting Unique Features of Microneedles to Modulate Immunity

et al. 2023

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“…Freeze drying of mRNA LNPs has been explored to enable storage at higher temperature, where both the type of cryoprotectants and the buffers used greatly impact the stability of mRNA LNPs. 333 Spikevax can be stored for 9 months at −50 °C to −15 °C and should be used within 14 days once thawed and stored at 2 °C to 8 °C. Zhang et al .…”

Section: Most Used Strategies To Prevent Degradation Of Clinically Ap...mentioning

confidence: 99%

Nucleic acid degradation as barrier to gene delivery: a guide to understand and overcome nuclease activity

Zhang,

Vandesompele,

Braeckmans

et al. 2024

Chem. Soc. Rev.

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“…Recent studies have shown promising results regarding the stability of mRNA-LNP formulations. Some formulations have demonstrated the ability to be lyophilized and stored at room temperature or even up to 37 °C for several weeks [ 39 , 40 ]. However, further validation is required to ensure reproducibility and reliability of these findings.…”

Section: Circumventing Limitations Of Lnp-mrna Covid-19 Vaccines With...mentioning

confidence: 99%

Engineered EVs with pathogen proteins: promising vaccine alternatives to LNP-mRNA vaccines

Zhang,

Sim,

Shen

et al. 2024

J Biomed Sci

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Extracellular vesicles (EVs) are tiny, lipid membrane-bound structures that are released by most cells. They play a vital role in facilitating intercellular communication by delivering bioactive cargoes to recipient cells and triggering cellular as well as biological responses. EVs have enormous potential for therapeutic applications as native or engineered exosomes. Native EVs are naturally released by cells without undergoing any modifications to either the exosomes or the cells that secrete them. In contrast, engineered EVs have been deliberately modified post-secretion or through genetic engineering of the secreting cells to alter their composition. Here we propose that engineered EVs displaying pathogen proteins could serve as promising alternatives to lipid nanoparticle (LNP)-mRNA vaccines. By leveraging their unique characteristics, these engineered EVs have the potential to overcome certain limitations associated with LNP-mRNA vaccines.

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Continuous freeze-drying of messenger RNA lipid nanoparticles enables storage at higher temperatures

Cited by 53 publications

References 51 publications

Exploiting Unique Features of Microneedles to Modulate Immunity

Exploiting Unique Features of Microneedles to Modulate Immunity

Nucleic acid degradation as barrier to gene delivery: a guide to understand and overcome nuclease activity

Engineered EVs with pathogen proteins: promising vaccine alternatives to LNP-mRNA vaccines

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