Evidence map›Paper›PMID 41164988›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

Replacing Helper Lipids With Cationic Lipids Enhances mRNA Lipid Nanoparticles Stability in Solution.

Rui Chen, Letao Xu, Nan Zhang, Haitao Yu, Xing Wang, Jiali Zhai, Fiona Whelan, Phillip Elliott, Chun-Xia Zhao

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. Article
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

9 authors.

Rui ChenSchool of Chemical Engineering, The University of Adelaide, Adelaide, South Australia, 5000, Australia.ORCID https://orcid.org/0000-0003-4671-4538
Letao XuSchool of Chemical Engineering, The University of Adelaide, Adelaide, South Australia, 5000, Australia.ORCID https://orcid.org/0000-0002-0449-8382
Nan ZhangSchool of Chemical Engineering, The University of Adelaide, Adelaide, South Australia, 5000, Australia.
Haitao YuSTEM College, RMIT University, Melbourne, Victoria, 3000, Australia.ORCID https://orcid.org/0000-0002-7700-2392
Xing WangSchool of Chemical Engineering, The University of Adelaide, Adelaide, South Australia, 5000, Australia.ORCID https://orcid.org/0000-0001-9166-5443
Jiali ZhaiSTEM College, RMIT University, Melbourne, Victoria, 3000, Australia.
Fiona WhelanAdelaide Microscopy, School of Biological Sciences, The University of Adelaide, Adelaide, South Australia, 5000, Australia.ORCID https://orcid.org/0000-0002-0791-6850
Phillip ElliottBioCina Pty Ltd, Adelaide, South Australia, 5031, Australia.
Chun-Xia ZhaoSchool of Chemical Engineering, The University of Adelaide, Adelaide, South Australia, 5000, Australia.ORCID https://orcid.org/0000-0002-3365-3759

Funding

Cooperative Research Centers Projects CRC-P) CXCPXII000132
6 · The paper itself

Abstract

Messenger RNA lipid nanoparticles (mRNA-LNPs) have achieved remarkable success in clinical vaccination efforts to curb the COVID-19 pandemic, and have attracted tremendous interest from both industry and academia to broaden their biomedical applications. However, their storage and transportation rely heavily on the cold chain to prevent rapid degradation in non-frozen solutions, posing significant challenges for logistics and accessibility. Therefore, enhancing the in-solution stability of mRNA LNPs is crucial. Herein, the role of helper phospholipids is investigated in storage stability of mRNA LNPs. By ratiometrically replacing the helper phospholipids (DSPC) with other alternative lipids (DOPS, DOTAP, and DOPE) in commercially available mRNA LNP formulation, enhanced in-solution stability was observed with cationic lipid (DOTAP) substitution at 42 °C, room temperature (22 °C), and 4 °C. Further correlation of stability with microstructure analysis using cryogenic electron microscopy revealed that partial replacement with DOTAP enhances structural stability by promoting the formation of intact LNPs and reducing the occurrence of "bleb"-like structures. Overall, the study provides insights into the structure-stability relationship in mRNA LNPs, and offers new strategies to address the storage limitations of mRNA-LNP products in the future.

Indexed as

LipidsNanoparticlesRNA, MessengerCationsCOVID-19HumansLiposomesSARS-CoV-2CationsLipid NanoparticlesLipidsLiposomesRNA, Messengercryogenic electron microscopylipid nanoparticlesmicrostructuremRNAstability study

Identifiers

PMID41164988
PMCPMC12806310

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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.