Evidence map›Paper›PMID 41811961›Full record

ArticleScience advances2026

Biodegradable targeted polymeric mRNA nanoparticles enable in vivo CD19 CAR T cell generation and lead to B cell depletion.

Manav Jain, Savannah E Est-Witte, Sydney R Shannon, Sarah Y Neshat, Xinjie Yu, Sydney Dunham, Tina Tian, Leonardo Cheng, Jawaun Harris, Maximilian F Konig and 3 more

Abstract read
In one paragraph

Article in Science advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
  2. Review
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  5. Review
  6. Editorial: Research on nanomaterials in tumor diagnosis and therapy, volume II.Frontiers in bioengineering and biotechnology · 2026
    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

13 authors.

Manav JainDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.ORCID 0000-0002-0933-490X
Savannah E Est-WitteDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.ORCID 0000-0003-3751-0760
Sydney R ShannonDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.ORCID 0000-0003-0474-0869
Sarah Y NeshatDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.ORCID 0000-0001-7849-5603
Xinjie YuInstitute for NanoBioTechnology, and Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.ORCID 0009-0003-3634-8551
Sydney DunhamDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Tina TianDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Leonardo ChengDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.ORCID 0000-0002-9214-8533
Jawaun HarrisDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Maximilian F KonigDivision of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
Stephany Y TzengDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.ORCID 0000-0002-7561-482X
Jonathan P SchneckDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.ORCID 0000-0001-5346-2776
Jordan J GreenDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.ORCID 0000-0003-4176-3808

Funding

TR&D Project 3P41EB028239 · NIBIB · JOHNS HOPKINS UNIVERSITY · PI Jamie Berta Spangler · 2019 to 2026
$11.5M
A PLATFORM TECHNOLOGY TO GENETICALLY REPROGRAM CANCER CELLS FOR ENHANCED IMMUNOTHERAPYR37CA246699 · NCI · JOHNS HOPKINS UNIVERSITY · PI TZENG, STEPHANY YI · 2020 to 2025
$2.6M
Kinetic Assembly of Polymer-mRNA Nanoparticles Targets Circulating Monocytes to Enhance Cancer ImmunotherapyR01CA281143 · NCI · JOHNS HOPKINS UNIVERSITY · PI Jordan Green, Hai-Quan Mao · 2023 to 2026
$2.3M
Precision immunotherapies targeting the 9G4 idiotype in lupus erythematosusR21AI176764 · NIAID · JOHNS HOPKINS UNIVERSITY · PI ANDRADE, FELIPE, KONIG, MAXIMILIAN FERDINAND · 2023 to 2024
$450k
Tolerance-Inducing mRNA Nanoparticles to Treat Type 1 DiabetesR56DK137420 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI DOLOFF, JOSHUA CHARLES, GREEN, JORDAN · 2023 to 2024
$442k
Tri-Signal Artificial Antigen Presenting Cells for Cancer ImmunotherapyF31CA284859 · NCI · JOHNS HOPKINS UNIVERSITY · PI SHANNON, SYDNEY ROSE · 2023 to 2025
$129k
NCI NIH HHS F31 CA284859NCI NIH HHS R01 CA281143NCI NIH HHS R37 CA246699NIAID NIH HHS R21 AI176764NIBIB NIH HHS P41 EB028239NIDDK NIH HHS R56 DK137420
6 · The paper itself

Abstract

While chimeric antigen receptor (CAR) T cell therapies have demonstrated therapeutic efficacy against B cell malignancies, widespread implementation of these therapies is hindered by a cumbersome, ex vivo manufacturing process. Delivery of CAR-encoding messenger RNA (mRNA) to endogenous T cells can generate these therapeutic cells in vivo and streamline this manufacturing workflow. To accomplish this, T cell-activating ligands were conjugated to a biodegradable polymeric mRNA nanoparticle to form T cell-targeted particles. By conjugating multiple activating ligands, T cell transfection and stimulation in vitro was increased, and greater T cell transfection and selectivity in vivo was achieved compared to an untargeted particle. These nanoparticles can flexibly encapsulate mRNA cargos and were used to deliver anti-CD19 CAR mRNA in vivo, enabling depletion of 95% of B cells in the peripheral blood and 50% depletion of splenic B cells in healthy mice. These findings regarding nanoparticle tropism and their potential therapeutic efficacy highlight the importance of this nonviral, polymeric platform to address key limitations associated with current CAR T practices.

Indexed as

Antigens, CD19B-LymphocytesImmunotherapy, AdoptiveLymphocyte DepletionNanoparticlesPolymersReceptors, Chimeric AntigenRNA, MessengerT-LymphocytesAnimalsHumansMiceAntigens, CD19PolymersReceptors, Chimeric AntigenRNA, Messenger

Identifiers

PMID41811961
PMCPMC12978253

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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.