Evidence map›Paper›PMID 34985952›Full record

ArticleScience advances2022

High-throughput and high-content bioassay enables tuning of polyester nanoparticles for cellular uptake, endosomal escape, and systemic in vivo delivery of mRNA.

Yuan Rui, David R Wilson, Stephany Y Tzeng, Hannah M Yamagata, Deepti Sudhakar, Marranne Conge, Cynthia A Berlinicke, Donald J Zack, Anthony Tuesca, Jordan J Green

Abstract read
In one paragraph

Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing 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

74 citing papers in PubMed.

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  5. Tissue-specific gene delivery approaches.Bioengineering & translational medicine · 2026
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14 more citing papers are in PubMed but not listed here.

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

10 authors.

Yuan RuiDepartment of Biomedical Engineering, Institute for NanoBioTechnology, and the Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0001-5165-8898
David R WilsonDepartment of Biomedical Engineering, Institute for NanoBioTechnology, and the Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0002-8708-4248
Stephany Y TzengDepartment of Biomedical Engineering, Institute for NanoBioTechnology, and the Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0002-7561-482X
Hannah M YamagataDepartment of Biomedical Engineering, Institute for NanoBioTechnology, and the Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Deepti SudhakarDepartment of Biomedical Engineering, Institute for NanoBioTechnology, and the Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0003-0125-796X
Marranne CongeDepartment of Biomedical Engineering, Institute for NanoBioTechnology, and the Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Cynthia A BerlinickeDepartment of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0003-1014-0800
Donald J ZackDepartment of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0002-7966-1973
Anthony TuescaAstraZeneca, Dosage Form and Design Development, BioPharmaceutical Development, BioPharmaceuticals R&D, Gaithersburg, MD, USA.ORCID 0000-0001-8048-7178
Jordan J GreenDepartment of Biomedical Engineering, Institute for NanoBioTechnology, and the Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0003-4176-3808

Funding

Wilmer Core Grant for Vision ResearchP30EY001765 · NEI · JOHNS HOPKINS UNIVERSITY · PI JEFFREY MUMM · 1985 to 2026
$22.1M
TR&D Project 3P41EB028239 · NIBIB · JOHNS HOPKINS UNIVERSITY · PI Jordan Green, JONATHAN P SCHNECK · 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
Suprachoroidal nonviral gene transfer of engineered VEGF antagonistsR01EY031097 · NEI · JOHNS HOPKINS UNIVERSITY · PI CAMPOCHIARO, PETER A, GREEN, JORDAN · 2020 to 2023
$2.4M
Gene Delivery Nanoparticles to Treat GlioblastomaR01CA228133 · NCI · JOHNS HOPKINS UNIVERSITY · PI GREEN, JORDAN · 2019 to 2023
$1.9M
High-throughput Optimization of Polymeric Nanoparticles for Small RNA Delivery to Treat GlioblastomaF31CA250319 · NCI · JOHNS HOPKINS UNIVERSITY · PI RUI, YUAN · 2020 to 2021
$46k
NCI NIH HHS F31 CA250319NCI NIH HHS R01 CA228133NCI NIH HHS R37 CA246699NEI NIH HHS P30 EY001765NEI NIH HHS R01 EY031097NIBIB NIH HHS P41 EB028239
6 · The paper itself

Abstract

Nanoparticle-based mRNA therapeutics hold great promise, but cellular internalization and endosomal escape remain key barriers for cytosolic delivery. We developed a dual nanoparticle uptake and endosomal disruption assay using high-throughput and high-content image-based screening. Using a genetically encoded Galectin 8 fluorescent fusion protein sensor, endosomal disruption could be detected via sensor clustering on damaged endosomal membranes. Simultaneously, nucleic acid endocytosis was quantified using fluorescently tagged mRNA. We used an array of biodegradable poly(beta-amino ester)s as well as Lipofectamine and PEI to demonstrate that this assay has higher predictive capacity for mRNA delivery compared to conventional polymer and nanoparticle physiochemical characteristics. Top nanoparticle formulations enabled safe and efficacious mRNA expression in multiple tissues following intravenous injection, demonstrating that the in vitro screening method is also predictive of in vivo performance. Efficacious nonviral systemic delivery of mRNA with biodegradable particles opens up new avenues for genetic medicine and human health.

Identifiers

PMID34985952
PMCPMC8730632

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.