Evidence map›Paper›PMID 41027853›Full record

ArticleNature communications2025

Protein corona formed on lipid nanoparticles compromises delivery efficiency of mRNA cargo.

Elizabeth Voke, Mariah L Arral, Henry J Squire, Teng-Jui Lin, Lining Zheng, Roxana Coreas, Alison Lui, Anthony T Iavarone, Rebecca L Pinals, Kathryn A Whitehead and 1 more

Abstract read
PubMed Full text at PMC Publisher
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 60 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed, 1 pooled it
–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

60 citing papers in PubMed, 1 synthesis or guideline pooled it.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Elizabeth VokeDepartment of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0001-6980-2632
Mariah L ArralDepartment of Chemical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA.
Henry J SquireDepartment of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-7125-6885
Teng-Jui LinDepartment of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-4691-1059
Lining ZhengDepartment of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, CA, USA.
Roxana CoreasDepartment of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, CA, USA.
Alison LuiDepartment of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, CA, USA.
Anthony T IavaroneCalifornia Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA, USA.
Rebecca L PinalsPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA. rpinals@stanford.edu.ORCID http://orcid.org/0000-0002-5369-2317
Kathryn A WhiteheadDepartment of Chemical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA. kawhite@cmu.edu.ORCID http://orcid.org/0000-0002-0100-7824
Markita P LandryDepartment of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, CA, USA. landry@berkeley.edu.ORCID http://orcid.org/0000-0002-5832-8522

Funding

High Definition Ion Mobility SpectrometerS10OD020062 · OD · UNIVERSITY OF CALIFORNIA BERKELEY · PI WILLIAMS, EVAN R · 2015 to 2015
$590k
Effects of Age on Lipid Nanoparticle Delivery and mRNA VaccinationF31AG077874 · NIA · CARNEGIE-MELLON UNIVERSITY · PI ARRAL, MARIAH · 2023 to 2024
$89k
National Science Foundation (NSF) 2046159NIA NIH HHS F31 AG077874NIH HHS S10 OD020062
6 · The paper itself

Abstract

Lipid nanoparticles (LNPs) are the most clinically advanced nonviral RNA-delivery vehicles, though challenges remain in fully understanding how LNPs interact with biological systems. In vivo, proteins form an associated corona on LNPs that redefines their physicochemical properties and influences delivery outcomes. Despite its importance, the LNP protein corona is challenging to study owing to the technical difficulty of selectively recovering soft nanoparticles from biological samples. Herein, we develop a quantitative, label-free mass spectrometry-based proteomics approach to characterize the protein corona on LNPs. Critically, this protein corona isolation workflow avoids artifacts introduced by the presence of endogenous nanoparticles in human biofluids. We apply continuous density gradient ultracentrifugation for protein-LNP complex isolation, with mass spectrometry for protein identification normalized to protein composition in the biofluid alone. With this approach, we quantify proteins consistently enriched in the LNP corona including vitronectin, C-reactive protein, and alpha-2-macroglobulin. We explore the impact of these corona proteins on cell uptake and mRNA expression in HepG2 human liver cells, and find that, surprisingly, increased levels of cell uptake do not correlate with increased mRNA expression in part due to protein corona-induced lysosomal trafficking of LNPs. Our results underscore the need to consider the protein corona in the design of LNP-based therapeutics.

Indexed as

LipidsNanoparticlesProtein CoronaRNA, MessengerHep G2 CellsHumansLiposomesMass SpectrometryProteomicsLipid NanoparticlesLipidsLiposomesProtein CoronaRNA, Messenger

Identifiers

PMID41027853
PMCPMC12485112

What OpenQuestion holds

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Registered trials

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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.