Evidence map›Paper›PMID 42056385›Full record

ArticleNature biotechnology2026

mRNA vaccine immunity is enhanced by hepatocyte detargeting and not dependent on dendritic cell expression.

Adam Marks, Sophia Siu, Filippo Bianchini, Chunxi Wang, Ashwitha Lakshmi, Matthew Phelan, Andrew Zhu, Chang Moon, Judit Morla-Folch, Abraham J P Teunissen and 6 more

Abstract read
In one paragraph

Article in Nature biotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Article
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  4. 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

16 authors.

Adam Marks *Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Sophia Siu *Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0002-1966-0100
Filippo BianchiniIcahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0002-0746-7629
Chunxi WangIcahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Ashwitha LakshmiIcahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Matthew PhelanIcahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Andrew ZhuTisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0009-0005-3089-7634
Chang MoonIcahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Judit Morla-FolchIcahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Abraham J P TeunissenIcahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Angelo AmabileIcahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Alessia BaccariniPrecision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Miriam MeradPrecision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0002-4481-7827
Joshua D BrodyIcahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0002-0850-6730
Yizhou DongIcahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0001-5786-0659
Brian D BrownIcahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. brian.brown@mssm.edu.ORCID http://orcid.org/0000-0002-3670-8778

Funding

cGMP Manufacture, Fill-Finish, Release, Analytical and Stability Testing and Stability Program of a Nanoparticle Based HIV Envelope Vaccine75N93022D00005 · NIAID · INTERNATIONAL AIDS VACCINE INITIATIVE · PI HASSELL, THOMAS · 2022 to 2025
$8.0M
Task Area A shall encompass annual follow-up of cohort members, clinical events investigations, study operations, and data analysis and manuscript writing. If implemented, Task A.1 will provide fundin75N92020D00005 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WATSON, KAROL E · 2020 to 2025
$5.1M
Translational Immunology Training ProgramT32AI078892 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Karen Leigh Edelblum, SERGIO A. LIRA · 2008 to 2026
$4.5M
Dissecting the pathways driving progenitor to pro-tumor macrophage programmingR01CA257195 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Brian D Brown, MIRIAM MERAD · 2021 to 2026
$3.3M
Development of novel lipid nanoparticles for nucleic acids delivery in the brainU01EB035521 · NIBIB · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Brian D Brown, Yizhou Dong · 2025 to 2026
$1.7M
microRNA-controlled mRNA therapeuticsR01DK138025 · NIDDK · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Brian D Brown · 2024 to 2026
$1.7M
Hepatocytes and skeletal myocytes shape immunity to mRNA-LNP encoded proteinF30AI194739 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Sophia Siu · 2025 to 2026
$106k
NCI NIH HHS R01 CA257195NHLBI NIH HHS 75N92020D00005NIAID NIH HHS 75N93022D00005NIAID NIH HHS F30 AI194739NIAID NIH HHS T32 AI078892NIBIB NIH HHS U01 EB035521NIDA NIH HHS 75N95020D00005NIDDK NIH HHS R01 DK138025NIH HHS 75N93023D00005NIH HHS 75N99020D00005U.S. Department of Health & Human Services | National Institutes of Health (NIH) F30AI194739U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01CA257195U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01DK138025U.S. Department of Health & Human Services | National Institutes of Health (NIH) T33AI078892U.S. Department of Health & Human Services | National Institutes of Health (NIH) U01EB035521
6 · The paper itself

Abstract

Proteins encoded by mRNA vaccines can be expressed by a diversity of transfected cell types but how cell-type-specific expression influences immunity is poorly understood. To investigate this, we incorporated synthetic microRNA target sites (miRT) into lipid nanoparticle (LNP)-delivered mRNA vaccines to silence mRNA expression specifically in professional antigen-presenting cells (pAPCs), hepatocytes or myocytes. We found that mRNA expression in pAPCs was dispensable for priming antigen-specific T cells, whereas mRNA expression in myocytes induced similar or stronger immune responses, including for SARS-CoV-2, suggesting that antigen cross-presentation or cross-dressing may be more impactful than direct mRNA expression in pAPCs. In contrast, mRNA expression in hepatocytes suppressed the antigen-specific T cell response, partly through PD1/PDL1. In mice bearing tumor-associated antigen (TAA)-expressing lymphoma cells, miRT-mediated hepatocyte-silenced TAA mRNA vaccine enhanced immune response and reduced tumor burden. Thus, non-pAPC expression shapes immunity to mRNA-encoded protein and inclusion of miRTs can boost or blunt mRNA-LNP immunogenicity.

Identifiers

PMID42056385
PMCPMC13552632

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.