Evidence map›Paper›PMID 33839230›Full record

ReviewInternational journal of pharmaceutics2021

mRNA-lipid nanoparticle COVID-19 vaccines: Structure and stability.

Linde Schoenmaker, Dominik Witzigmann, Jayesh A Kulkarni, Rein Verbeke, Gideon Kersten, Wim Jiskoot, Daan J A Crommelin

Open access · hybridAbstract readReview
In one paragraph

Review in International journal of pharmaceutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 707 papers.

0numbers the graph read from it
0cells of the map it votes in
707citing papers in PubMed
79.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

707 citing papers in PubMed, 1,403 citations in OpenAlex.

  1. Cas12a chRDNA-mediatedMolecular therapy. Nucleic acids · 2026
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  11. Towards mRNA therapeutics 2.0.Nature reviews. Drug discovery · 2026
    Review
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  14. Review
  15. Article
  16. Article
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  18. Dual pKa Lipid Nanoparticles for Lung-tropic mRNA Delivery and pH-Programmed Endosomal Escape.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  19. Article
  20. Review

647 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 3 countries.

Linde SchoenmakerDivision of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, 2300 RA Leiden, the Netherlands.
Dominik WitzigmannDepartment of Biochemistry and Molecular Biology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada; NanoMedicines Innovation Network (NMIN), University of British Columbia, Vancouver, BC, Canada.
Jayesh A KulkarniDepartment of Biochemistry and Molecular Biology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada; NanoMedicines Innovation Network (NMIN), University of British Columbia, Vancouver, BC, Canada.
Rein VerbekeGhent Research Group on Nanomedicines, Faculty of Pharmacy, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.
Gideon KerstenDivision of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, 2300 RA Leiden, the Netherlands; Coriolis Pharma, Fraunhoferstrasse 18b, 82152 Martinsried, Germany.
Wim JiskootDivision of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, 2300 RA Leiden, the Netherlands; Coriolis Pharma, Fraunhoferstrasse 18b, 82152 Martinsried, Germany. Electronic address: w.jiskoot@lacdr.leidenuniv.nl.
Daan J A CrommelinDepartment of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Utrecht, the Netherlands. Electronic address: d.j.a.crommelin@uu.nl.
Leiden University · NLUniversity of British Columbia · CAGhent University · BEUtrecht University · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

A drawback of the current mRNA-lipid nanoparticle (LNP) COVID-19 vaccines is that they have to be stored at (ultra)low temperatures. Understanding the root cause of the instability of these vaccines may help to rationally improve mRNA-LNP product stability and thereby ease the temperature conditions for storage. In this review we discuss proposed structures of mRNA-LNPs, factors that impact mRNA-LNP stability and strategies to optimize mRNA-LNP product stability. Analysis of mRNA-LNP structures reveals that mRNA, the ionizable cationic lipid and water are present in the LNP core. The neutral helper lipids are mainly positioned in the outer, encapsulating, wall. mRNA hydrolysis is the determining factor for mRNA-LNP instability. It is currently unclear how water in the LNP core interacts with the mRNA and to what extent the degradation prone sites of mRNA are protected through a coat of ionizable cationic lipids. To improve the stability of mRNA-LNP vaccines, optimization of the mRNA nucleotide composition should be prioritized. Secondly, a better understanding of the milieu the mRNA is exposed to in the core of LNPs may help to rationalize adjustments to the LNP structure to preserve mRNA integrity. Moreover, drying techniques, such as lyophilization, are promising options still to be explored.

Indexed as

COVID-19NanoparticlesCOVID-19 VaccinesHumansLipidsRNA, MessengerRNA, Small InterferingSARS-CoV-2COVID-19 VaccinesLipidsRNA, MessengerRNA, Small InterferingCOVID-19Lipid nanoparticle (LNP)LyophilizationmRNAShelf lifeStorage stabilityStructureVaccine

Identifiers

PMID33839230
PMCPMC8032477
OpenAlexW3148255637

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.