Evidence map›Paper›PMID 40319025›Full record

ArticleNature communications2025

Liposomal lipid nanoparticles for extrahepatic delivery of mRNA.

Miffy Hok Yan Cheng, Yao Zhang, Kevin Fox, Jerry Leung, Colton Strong, Emma Kang, Yihang Chen, Michelle Tong, Hemashree Bommadevara, Eric Jan and 7 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing 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

27 citing papers in PubMed.

  1. Article
  2. Review
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  6. Review
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  9. Article
  10. Investigating theBioconjugate chemistry · 2026
    Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. Review
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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

17 authors.

Miffy Hok Yan ChengDepartment of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada. miffy.cheng@ubc.ca.ORCID http://orcid.org/0000-0002-0261-4642
Yao ZhangDepartment of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada.
Kevin FoxDepartment of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada.
Jerry LeungDepartment of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada.ORCID http://orcid.org/0000-0002-8714-8440
Colton StrongDepartment of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada.ORCID http://orcid.org/0000-0003-4031-9932
Emma KangDepartment of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada.
Yihang ChenDepartment of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada.
Michelle TongDepartment of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada.
Hemashree BommadevaraDepartment of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada.
Eric JanDepartment of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada.ORCID http://orcid.org/0000-0003-0523-8467
Owen Yuk Long IpPolymorphic BioSciences, Vancouver, BC, Canada.
Cristina Rodríguez-RodríguezFaculty of Pharmaceutical Sciences, 2405 Wesbrook Mall, Vancouver, BC, Canada.ORCID http://orcid.org/0000-0002-3313-4422
Katayoun SaatchiFaculty of Pharmaceutical Sciences, 2405 Wesbrook Mall, Vancouver, BC, Canada.
Urs O HäfeliFaculty of Pharmaceutical Sciences, 2405 Wesbrook Mall, Vancouver, BC, Canada.ORCID http://orcid.org/0000-0003-0671-4509
Amir AbdolahzadehNanoVation Therapeutics Inc., 2405 Wesbrook Mall, Vancouver, BC, Canada.
Dominik WitzigmannDepartment of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada.
Pieter R CullisDepartment of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada. pieterc@mail.ubc.ca.ORCID http://orcid.org/0000-0001-9586-2508

Funding

Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) FDN 148469
6 · The paper itself

Abstract

Long-circulating, transfection-competent lipid nanoparticle (LNP)-mRNA delivery systems are critical for achieving efficient transfection in extrahepatic tissues. Here we investigate the properties of LNP mRNA systems containing high proportions of bilayer forming lipids, using equimolar egg sphingomyelin and cholesterol as the bilayer-forming components. We show that LNP mRNA systems prepared at bilayer lipid to ionizable lipid molar ratios of 4-0.67 exhibit high mRNA encapsulation efficiencies (90-100%) and excellent transfection potencies in vitro. Systems with bilayer lipid to ionizable lipid molar ratios equating to 4 exhibit a liposomal morphology with a solid core suspended in an aqueous interior surrounded by a lipid bilayer. These liposomal LNPs exhibit longer circulation lifetimes than LNP systems with Onpattro-like lipid compositions and have enhanced extrahepatic transfection properties. The prolonged blood circulation lifetime is attributed to reduced plasma protein adsorption. The transfection competency of liposomal LNP systems is attributed to export of the solid core containing mRNA from the LNP as the endosomal pH is lowered.

Indexed as

LipidsLiposomesNanoparticlesRNA, MessengerTransfectionAnimalsCholesterolHumansLipid BilayersMiceSphingomyelinsCholesterolLipid BilayersLipidsLiposomesRNA, MessengerSphingomyelins

Identifiers

PMID40319025
PMCPMC12049435

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.