Evidence map›Paper›PMID 36351479›Full record

ReviewJournal of pharmaceutical sciences2023

The Storage and In-Use Stability of mRNA Vaccines and Therapeutics: Not A Cold Case.

Erik Oude Blenke, Eivor Örnskov, Christian Schöneich, Gunilla A Nilsson, David B Volkin, Enrico Mastrobattista, Örn Almarsson, Daan J A Crommelin

Open access · hybridAbstract readReview
In one paragraph

Review in Journal of pharmaceutical sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed
13.9field-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

92 citing papers in PubMed, 177 citations in OpenAlex.

  1. Review
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  4. Effect of CaClACS omega · 2026
    Article
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  8. Acta pharmaceutica Sinica. B · 2026
    Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Decoding Undesirable Inflammatory Responses of Nucleic Acid-Delivering Lipid Nanoparticles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Review

32 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

8 authors at 6 institutions in 6 countries.

Erik Oude BlenkeAdvanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, 43183 Gothenburg, Sweden. Electronic address: E.OudeBlenke@astrazeneca.com.
Eivor ÖrnskovAdvanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, 43183 Gothenburg, Sweden. Electronic address: eivor.ornskov@astrazeneca.com.
Christian SchöneichDepartment of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66047 United States. Electronic address: schoneic@ku.edu.
Gunilla A NilssonAdvanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, 43183 Gothenburg, Sweden. Electronic address: gunilla.a.nilsson@astrazeneca.com.
David B VolkinDepartment of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66047 United States; Vaccine Analytics and Formulation Center, University of Kansas, Lawrence, KS 66047 United States. Electronic address: volkin@ku.edu.
Enrico MastrobattistaDepartment of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, the Netherlands. Electronic address: e.mastrobattista@uu.nl.
Örn AlmarssonAfiRx LLC, Chestnut Hill, MA 02467 United States; Visiting Fellow, UNSW RNA Institute and the School of Chemistry, UNSW, Sydney, Australia. Electronic address: orn@afirx.com.
Daan J A CrommelinDepartment of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, the Netherlands. Electronic address: d.j.a.crommelin@uu.nl.
University of Kansas · USUtrecht University · NLAstraZeneca (Netherlands) · NLAstraZeneca (Singapore) · SGAstraZeneca (Sweden) · SEChestnut Hill College · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The remarkable impact of mRNA vaccines on mitigating disease and improving public health has been amply demonstrated during the COVID-19 pandemic. Many new mRNA-based vaccine and therapeutic candidates are in development, yet the current reality of their stability limitations requires their frozen storage. Numerous challenges remain to improve formulated mRNA stability and enable refrigerator storage, and this review provides an update on developments to tackle this multi-faceted stability challenge. We describe the chemistry underlying mRNA degradation during storage and highlight how lipid nanoparticle (LNP) formulations are a double-edged sword: while LNPs protect mRNA against enzymatic degradation, interactions with and between LNP excipients introduce additional risks for mRNA degradation. We also discuss strategies to improve mRNA stability both as a drug substance (DS) and a drug product (DP) including the (1) design of the mRNA molecule (nucleotide selection, primary and secondary structures), (2) physical state of the mRNA-LNP complexes, (3) formulation composition and purity of the components, and (4) DS and DP manufacturing processes. Finally, we summarize analytical control strategies to monitor and assure the stability of mRNA-based candidates, and advocate for an integrated analytical and formulation development approach to further improve their storage, transport, and in-use stability profiles.

Indexed as

COVID-19NanoparticlesHumansLipidsLiposomesmRNA VaccinesPandemicsRNA, MessengerLipidsLiposomesmRNA VaccinesRNA, MessengerDegradation mechanismsFormulationImpuritiesIonizable lipidLipid nanoparticlesLNPmRNA structurePhysical and chemical analysisShelf lifeStabilityVaccine

Identifiers

PMID36351479
PMCPMC9637289
OpenAlexW4308293505

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.