Evidence map›Paper›PMID 38730092›Full record

ArticleCommunications biology2024

Overcoming thermostability challenges in mRNA-lipid nanoparticle systems with piperidine-based ionizable lipids.

Kazuki Hashiba, Masamitsu Taguchi, Sachiko Sakamoto, Ayaka Otsu, Yoshiki Maeda, Hirofumi Ebe, Arimichi Okazaki, Hideyoshi Harashima, Yusuke Sato

Abstract read
In one paragraph

Article in Communications biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing 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

43 citing papers in PubMed.

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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.

Kazuki HashibaNucleic Acid Medicine Business Division, Nitto Denko Corporation, 1-1-2, Shimohozumi, Ibaraki, Osaka, 567-8680, Japan. kazuki.hashiba@nitto.com.ORCID 0000-0002-1434-0773
Masamitsu TaguchiNucleic Acid Medicine Business Division, Nitto Denko Corporation, 1-1-2, Shimohozumi, Ibaraki, Osaka, 567-8680, Japan.
Sachiko SakamotoNucleic Acid Medicine Business Division, Nitto Denko Corporation, 1-1-2, Shimohozumi, Ibaraki, Osaka, 567-8680, Japan.
Ayaka OtsuNucleic Acid Medicine Business Division, Nitto Denko Corporation, 1-1-2, Shimohozumi, Ibaraki, Osaka, 567-8680, Japan.
Yoshiki MaedaNucleic Acid Medicine Business Division, Nitto Denko Corporation, 1-1-2, Shimohozumi, Ibaraki, Osaka, 567-8680, Japan.
Hirofumi EbeNucleic Acid Medicine Business Division, Nitto Denko Corporation, 1-1-2, Shimohozumi, Ibaraki, Osaka, 567-8680, Japan.
Arimichi OkazakiNucleic Acid Medicine Business Division, Nitto Denko Corporation, 1-1-2, Shimohozumi, Ibaraki, Osaka, 567-8680, Japan.
Hideyoshi HarashimaLaboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-Ku, Sapporo, 060-0812, Japan.ORCID 0000-0002-1568-9547
Yusuke SatoLaboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-Ku, Sapporo, 060-0812, Japan. y_sato@pharm.hokudai.ac.jp.ORCID 0000-0003-0913-7815

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Lipid nanoparticles (LNPs) have emerged as promising platforms for efficient in vivo mRNA delivery owing to advancements in ionizable lipids. However, maintaining the thermostability of mRNA/LNP systems remains challenging. While the importance of only a small amount of lipid impurities on mRNA inactivation is clear, a fundamental solution has not yet been proposed. In this study, we investigate an approach to limit the generation of aldehyde impurities that react with mRNA nucleosides through the chemical engineering of lipids. We demonstrated that piperidine-based lipids improve the long-term storage stability of mRNA/LNPs at refrigeration temperature as a liquid formulation. High-performance liquid chromatography analysis and additional lipid synthesis revealed that amine moieties of ionizable lipids play a vital role in limiting reactive aldehyde generation, mRNA-lipid adduct formation, and loss of mRNA function during mRNA/LNP storage. These findings highlight the importance of lipid design and help enhance the shelf-life of mRNA/LNP systems.

Indexed as

LipidsNanoparticlesPiperidinesRNA, MessengerRNA StabilityHumansLiposomesTemperatureLipid NanoparticlesLipidsLiposomespiperidinePiperidinesRNA, Messenger

Identifiers

PMID38730092
PMCPMC11087515

What OpenQuestion holds

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LicenceCC BY
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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.