Evidence map›Paper›PMID 41184608›Full record

ArticleNature biomedical engineering2026

A microphysiological system for screening lipid nanoparticle-mRNA complexes predicts in vivo heart transfection efficacy.

Gabriel Neiman, Mauro W Costa, Hesong Han, Sheng Zhao, Tammy K Ng, Brian Siemons, Tomohiro Nishino, Yu Huang, Shyam Lal, Kenneth Wu and 5 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature biomedical engineering, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. New approach methodologies (NAMs) for preclinical and translational evaluation of mRNA-lipid nanoparticle (LNP) therapeutics.Journal of controlled release : official journal of the Controlled Release Society · 2026
    Review
  3. Review
  4. 2025 in review.Nature biomedical engineering · 2025
    Article
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

15 authors.

Gabriel NeimanDepartment of Bioengineering, California Institute for Quantitative Biosciences (QB3), University of California at Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0003-1003-1559
Mauro W CostaGladstone Institutes, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-3579-8625
Hesong HanDepartment of Bioengineering, California Institute for Quantitative Biosciences (QB3), University of California at Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0001-5545-5238
Sheng ZhaoDepartment of Bioengineering, California Institute for Quantitative Biosciences (QB3), University of California at Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0009-0002-9890-048X
Tammy K NgDepartment of Materials Science and Engineering, University of California at Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0003-1338-0025
Brian SiemonsDepartment of Bioengineering, California Institute for Quantitative Biosciences (QB3), University of California at Berkeley, Berkeley, CA, USA.
Tomohiro NishinoGladstone Institutes, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-3593-7368
Yu HuangGladstone Institutes, San Francisco, CA, USA.
Shyam LalGladstone Institutes, San Francisco, CA, USA.
Kenneth WuGladstone Institute of Cardiovascular Disease, San Francisco, CA, USA.
Luke M JudgeGladstone Institute of Cardiovascular Disease, San Francisco, CA, USA.
Bruce R ConklinGladstone Institute of Cardiovascular Disease, San Francisco, CA, USA.
Deepak SrivastavaGladstone Institutes, San Francisco, CA, USA. deepak.srivastava@gladstone.ucsf.edu.ORCID http://orcid.org/0000-0002-3480-5953
Niren MurthyDepartment of Bioengineering, California Institute for Quantitative Biosciences (QB3), University of California at Berkeley, Berkeley, CA, USA. nmurthy@berkeley.edu.ORCID http://orcid.org/0000-0002-7815-7337
Kevin E HealyDepartment of Bioengineering, California Institute for Quantitative Biosciences (QB3), University of California at Berkeley, Berkeley, CA, USA. kehealy@berkeley.edu.ORCID http://orcid.org/0000-0002-8524-3671

Funding

California Institute for Regenerative Medicine (CIRM) DISC2-14045
6 · The paper itself

Abstract

Gene transfection via lipid nanoparticle (LNP)-mRNA complexes have tremendous potential for treating cardiac diseases. However, the transfection efficiency is poor and there is a lack of in vitro screening systems that predict transfection efficacy. Here we demonstrate a method for identifying LNP-mRNA complexes that diffuse efficiently within 3D cardiac micromuscles and transfect cardiomyocytes with high efficiency, using a phenotypic cardiac microphysiological system (MPS) constructed from a human induced pluripotent stem cell cardiomyocytes Cre-reporter line. LNP formulations containing an acid-degradable PEG-lipid had enhanced diffusion and gene editing efficiency in the cardiac MPS. The in vivo delivery of LNP-mRNA complexes, including luciferase and CRE mRNA, into Ai6 mice confirmed the cardiac MPS screening outcomes. Acid-degradable PEG-LNPs achieved notably superior transfection in the heart with reduced off-target liver uptake compared with standard LNP formulations. The cardiac MPS showed strong LNP transfection in vitro and pinpointed a promising formulation for in vivo mRNA delivery to the heart.

Indexed as

LipidsMyocardiumNanoparticlesRNA, MessengerTransfectionAnimalsHumansLiposomesMiceMicrophysiological SystemsMyocytes, CardiacPolyethylene GlycolsLipid NanoparticlesLipidsLiposomesPolyethylene GlycolsRNA, Messenger

Identifiers

PMID41184608

What Socratic holds

Textmetadata
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 Socratic graph.