Evidence map›Paper›PMID 41603124›Full record

ArticleAdvanced materials (Deerfield Beach, Fla.)2026

High-Throughput In Vivo Screening Using Barcoded mRNA Identifies Lipid Nanoparticles With Extrahepatic Tropism for In Situ Immunoengineering.

Alex G Hamilton, Ajay S Thatte, Junchao Xu, Zhangyi Luo, Hannah C Safford, Kelsey L Swingle, Jenna Muscat-Rivera, Michael Kegel, Xuexiang Han, Ryann A Joseph and 8 more

Abstract read
In one paragraph

Article in Advanced materials (Deerfield Beach, Fla.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

18 authors.

Alex G HamiltonDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Ajay S ThatteDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Junchao XuDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Zhangyi LuoDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Hannah C SaffordDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Kelsey L SwingleDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Jenna Muscat-RiveraDepartment of Medicine, Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Michael KegelDepartment of Medicine, Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Xuexiang HanDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Ryann A JosephDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Amanda M MurrayDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Hannah C GeislerDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Ricardo C WhitakerDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Lulu XueDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Roman SpektorField of Genetics, Genomics, and Development, Cornell University, Ithaca, New York, USA.
Jilian R MelamedDepartment of Medicine, Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Drew WeissmanDepartment of Medicine, Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Michael J MitchellDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.ORCID 0000-0002-3628-2244

Funding

A data-driven drug delivery (4D) platform for probing and treating the chemoresistant bone marrow microenvironmentDP2TR002776 · NCATS · UNIVERSITY OF PENNSYLVANIA · PI MITCHELL, MICHAEL J · 2018 to 2018
$2.4M
mRNA lipid nanoparticles for pre-eclampsiaR01HD115877 · NICHD · UNIVERSITY OF PENNSYLVANIA · PI Michael J Mitchell · 2024 to 2026
$1.0M
Abramson Cancer Center P30 016520Burroughs Wellcome FundNational Science Foundation CBET-2145491NCATS NIH HHS DP2 TR002776NICHD NIH HHS R01 HD115877NIH HHS DP2 TR002776NSF GRFP fellowships
6 · The paper itself

Abstract

Interest continues to grow in the use of mRNA vaccines and therapeutics. While effective for immunization against infectious diseases, lipid nanoparticle (LNP) formulations used for other mRNA delivery applications suffer from off-target accumulation, poor immune transfection, and reactogenicity, limiting their application to immunoengineering. Development of new mRNA LNPs is severely bottlenecked by the LNP discovery process, which is historically low-throughput due to reliance on low-plex measurements. Here, we develop a high-throughput in vivo mRNA LNP screening platform based on barcoded mRNA (b-mRNA). Using this b-mRNA screening platform to simultaneously evaluate 122 LNPs, we identify novel LNP formulations capable of potent hepatic and extrahepatic transfection. We evaluate a lead LNP candidate for in situ immune modulation in a syngeneic mouse model of melanoma and demonstrate a significant reduction in tumor burden and extended survival compared to mice treated with a gold standard mRNA LNP formulation. We employ novel biochemical characterization techniques to analyze nanoparticle protein corona formation with single-particle resolution and gain insight into the influence of protein adsorption on hepatic and splenic transfection. Together, our results demonstrate the value of advanced LNP screening and characterization techniques for the development of next-generation mRNA LNPs for immunoengineering.

Indexed as

High-Throughput Screening AssaysLipidsNanoparticlesRNA, MessengerAnimalsCell Line, TumorFemaleLiposomesLiverMiceTransfectionLipid NanoparticlesLipidsLiposomesRNA, Messengerbarcodehigh‐throughput screeninglipid nanoparticlemRNAnanoparticle

Identifiers

PMID41603124
PMCPMC12957869

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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.