Evidence map›Paper›PMID 31551417›Full record

ArticleNature communications2019

Linkage between endosomal escape of LNP-mRNA and loading into EVs for transport to other cells.

Marco Maugeri, Muhammad Nawaz, Alexandros Papadimitriou, Annelie Angerfors, Alessandro Camponeschi, Manli Na, Mikko Hölttä, Pia Skantze, Svante Johansson, Martina Sundqvist and 8 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 220 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
220citing papers in PubMed, 1 pooled it
12.6field-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

220 citing papers in PubMed, 1 synthesis or guideline pooled it, 403 citations in OpenAlex.

  1. Pooled it
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  7. Article
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  13. Article
  14. Decoding Undesirable Inflammatory Responses of Nucleic Acid-Delivering Lipid Nanoparticles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  15. Review
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  18. Article
  19. Review
  20. Optimizing C14120-based LNPs forMolecular therapy. Nucleic acids · 2026
    Article

160 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

18 authors at 2 institutions in 1 country.

Marco MaugeriDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 46, Gothenburg, Sweden.ORCID http://orcid.org/0000-0003-2157-1542
Muhammad NawazDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 46, Gothenburg, Sweden.ORCID http://orcid.org/0000-0002-0792-8296
Alexandros PapadimitriouDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 46, Gothenburg, Sweden.
Annelie AngerforsAdvanced Drug Delivery, Pharmaceutical Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, 431 83, Mölndal, Sweden.ORCID http://orcid.org/0000-0001-6631-1977
Alessandro CamponeschiDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 46, Gothenburg, Sweden.
Manli NaDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 46, Gothenburg, Sweden.
Mikko HölttäTranslational Biomarkers and Bioanalysis, Clinical Pharmacology & Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, 431 83, Mölndal, Sweden.
Pia SkantzeAdvanced Drug Delivery, Pharmaceutical Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, 431 83, Mölndal, Sweden.
Svante JohanssonAdvanced Drug Delivery, Pharmaceutical Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, 431 83, Mölndal, Sweden.
Martina SundqvistDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 46, Gothenburg, Sweden.ORCID http://orcid.org/0000-0002-0859-0792
Johnny LindquistTranslational Biomarkers and Bioanalysis, Clinical Pharmacology & Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, 431 83, Mölndal, Sweden.
Tomas KjellmanAdvanced Drug Delivery, Pharmaceutical Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, 431 83, Mölndal, Sweden.
Inga-Lill MårtenssonDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 46, Gothenburg, Sweden.
Tao JinDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 46, Gothenburg, Sweden.ORCID http://orcid.org/0000-0001-9039-0628
Per SunnerhagenDepartment of Chemistry and Molecular Biology, University of Gothenburg, Box 462, 405 30, Gothenburg, Sweden.ORCID http://orcid.org/0000-0002-0967-8729
Sofia ÖstmanAnimal Sciences and Technologies, Clinical Pharmacology & Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, 431 83, Mölndal, Sweden.
Lennart LindforsAdvanced Drug Delivery, Pharmaceutical Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, 431 83, Mölndal, Sweden.
Hadi ValadiDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 46, Gothenburg, Sweden. hadi.valadi@gu.se.ORCID http://orcid.org/0000-0003-3482-2451
University of Gothenburg · SEAstraZeneca (Sweden) · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

RNA-based therapeutics hold great promise for treating diseases and lipid nanoparticles (LNPs) represent the most advanced platform for RNA delivery. However, the fate of the LNP-mRNA after endosome-engulfing and escape from the autophagy-lysosomal pathway remains unclear. To investigate this, mRNA (encoding human erythropoietin) was delivered to cells using LNPs, which shows, for the first time, a link between LNP-mRNA endocytosis and its packaging into extracellular vesicles (endo-EVs: secreted after the endocytosis of LNP-mRNA). Endosomal escape of LNP-mRNA is dependent on the molar ratio between ionizable lipids and mRNA nucleotides. Our results show that fractions of ionizable lipids and mRNA (1:1 molar ratio of hEPO mRNA nucleotides:ionizable lipids) of endocytosed LNPs were detected in endo-EVs. Importantly, these EVs can protect the exogenous mRNA during in vivo delivery to produce human protein in mice, detected in plasma and organs. Compared to LNPs, endo-EVs cause lower expression of inflammatory cytokines.

Indexed as

Lipid MetabolismAnimalsBiological TransportCell LineCytoplasmEndosomesErythropoietinExtracellular VesiclesFemaleHumansLipidsMiceMice, Inbred C57BLNanoparticlesRNA, MessengerEPO protein, humanErythropoietinLipidsRNA, Messenger

Identifiers

PMID31551417
PMCPMC6760118
OpenAlexW2975259971

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.