Evidence map›Paper›PMID 41844984›Full record

ArticleNature materials2026

Crosslinked ionizable lipids reprogram dendritic cell metabolism for potent mRNA vaccination.

Dongyoon Kim, Ningqiang Gong, Mohamad-Gabriel Alameh, Emily L Han, Hanxun Wang, Jinjin Wang, Ellie Feng, Il-Chul Yoon, Amanda M Murray, Qiangqiang Shi and 4 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature materials, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
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

14 authors.

Dongyoon Kim *Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
Ningqiang Gong *Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-9444-8505
Mohamad-Gabriel AlamehDepartment of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-5672-6930
Emily L HanDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0009-0008-6276-7502
Hanxun WangDepartment Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, China.
Jinjin WangDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-8382-044X
Ellie FengDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0009-0002-4900-4814
Il-Chul YoonDepartment of Chemistry, University of Pennsylvania, Philadelphia, PA, USA.
Amanda M MurrayDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0009-0000-2124-351X
Qiangqiang ShiDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0009-0009-2503-4374
So-Jeong MoonDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-6247-0855
Kaitlin MrksichDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0009-0008-7971-2129
Drew WeissmanPenn Institute for RNA Innovation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-1501-6510
Michael J MitchellDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA. mjmitch@seas.upenn.edu.ORCID http://orcid.org/0000-0002-3628-2244

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Modulating metabolism in immune cells is an effective approach to induce desired immune responses. Here we develop a lipid nanoparticle (LNP) capable of metabolic reprogramming of dendritic cells for mRNA vaccine applications. Using imidoester-based conjugation chemistry, we design a crosslinked ionizable lipid, C12-2aN, which possesses intrinsic metabolic modulatory properties. This multifunctional ionizable lipid not only promotes effective mRNA expression by facilitating endosomal escape but also stimulates glycolysis through mTORC2 pathway activation. As both an mRNA carrier and a metabolic modulator, C12-2aN LNPs lead to potent vaccine efficacy in both SARS-CoV-2 and OVA cancer vaccine models, resulting in stronger neutralization of pseudovirus infection and improved survival rates, respectively, compared with control LNPs without the crosslinker. Moreover, C12-2aN LNPs outperformed FDA-approved LNPs in terms of reduced off-target delivery and lower immunogenicity. Overall, the integration of mRNA delivery and metabolic reprogramming induced by the ionizable lipid component presents significant potential for next-generation mRNA LNP vaccines.

Identifiers

PMID41844984

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.