Evidence map›Paper›PMID 38491873›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024

In Vitro Transcribed mRNA Immunogenicity Induces Chemokine-Mediated Lymphocyte Recruitment and Can Be Gradually Tailored by Uridine Modification.

Norman M Drzeniek, Nourhan Kahwaji, Samira Picht, Ioanna Maria Dimitriou, Stephan Schlickeiser, Hanieh Moradian, Sven Geissler, Michael Schmueck-Henneresse, Manfred Gossen, Hans-Dieter Volk

Open access · goldAbstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
3.7field-weighted citation impact, top 6% 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

15 citing papers in PubMed, 16 citations in OpenAlex.

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  6. Delivery platforms forFrontiers in immunology · 2026
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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

10 authors at 3 institutions in 1 country.

Norman M DrzeniekCharité - Universitätsmedizin Berlin, corporate member of Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin, Institute of Medical Immunology, Augustenburger Platz 1, 13353, Berlin, Germany.ORCID 0000-0001-6562-2351
Nourhan KahwajiBerlin Institute of Health at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Föhrer Straße 15, 13353, Berlin, Germany.ORCID 0000-0002-9326-8529
Samira PichtBerlin Institute of Health at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Föhrer Straße 15, 13353, Berlin, Germany.
Ioanna Maria DimitriouBerlin Institute of Health at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Föhrer Straße 15, 13353, Berlin, Germany.
Stephan SchlickeiserCharité - Universitätsmedizin Berlin, corporate member of Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin, Institute of Medical Immunology, Augustenburger Platz 1, 13353, Berlin, Germany.
Hanieh MoradianInstitute of Active Polymers, Helmholtz-Zentrum Hereon, Kantstraße 55, 14513, Teltow, Germany.
Sven GeisslerBerlin Institute of Health at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Föhrer Straße 15, 13353, Berlin, Germany.
Michael Schmueck-HenneresseBerlin Institute of Health at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Föhrer Straße 15, 13353, Berlin, Germany.
Manfred GossenInstitute of Active Polymers, Helmholtz-Zentrum Hereon, Kantstraße 55, 14513, Teltow, Germany.
Hans-Dieter VolkCharité - Universitätsmedizin Berlin, corporate member of Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin, Institute of Medical Immunology, Augustenburger Platz 1, 13353, Berlin, Germany.
Berlin-Brandenburger Centrum für Regenerative Therapien · DEBerlin Institute of Health at Charité - Universitätsmedizin Berlin · DEHumboldt-Universität zu Berlin · DE

Funding

Einstein Foundation Berlin Advanced_Scientist_KickboxEuropean Health and Digital Executive Agency 101095635-PROTOGerman Federal Ministry of Education and Research 031L0234BGerman Federal Ministry of Education and Research 13GW0098German Federal Ministry of Education and Research 13GW0099German Research Foundation CollaborativeResearchCenter1444(CRC1444)Horizon 2020 Framework Programme 733006Horizon 2020 Framework Programme 779293
6 · The paper itself

Abstract

Beyond SARS-CoV2 vaccines, mRNA drugs are being explored to overcome today's greatest healthcare burdens, including cancer and cardiovascular disease. Synthetic mRNA triggers immune responses in transfected cells, which can be reduced by chemically modified nucleotides. However, the side effects of mRNA-triggered immune activation on cell function and how different nucleotides, such as the N1-methylpseudouridine (m1Ψ) used in SARS-CoV2 vaccines, can modulate cellular responses is not fully understood. Here, cellular responses toward a library of uridine-modified mRNAs are investigated in primary human cells. Targeted proteomics analyses reveal that unmodified mRNA induces a pro-inflammatory paracrine pattern marked by the secretion of chemokines, which recruit T and B lymphocytes toward transfected cells. Importantly, the magnitude of mRNA-induced changes in cell function varies quantitatively between unmodified, Ψ-, m1Ψ-, and 5moU-modified mRNA and can be gradually tailored, with implications for deliberately exploiting this effect in mRNA drug design. Indeed, both the immunosuppressive effect of stromal cells on T-cell proliferation, and the anti-inflammatory effect of IL-10 mRNA are enhanced by appropriate uridine modification. The results provide new insights into the effects of mRNA drugs on cell function and cell-cell communication and open new possibilities to tailor mRNA-triggered immune activation to the desired pro- or anti-inflammatory application.

Indexed as

RNA, MessengerUridineCells, CulturedChemokinesCOVID-19HumansT-LymphocytesChemokinesRNA, MessengerUridine5‐methoxyuridineCXCL10immunoengineeringinnate immune activationN1‐methylpseudouridinenucleoside‐modified messenger RNAT cell migration

Identifiers

PMID38491873
PMCPMC11151007
OpenAlexW4392880886

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.