Evidence map›Paper›PMID 42230627›Full record

ArticleNature communications2026

Trivalent ions kinetic-gating for producing high-concentration and shelf-stable plasmid DNA/PEI particles.

Jinghan Lin, Yizong Hu, Turash H Pial, Kailei D Goodier, Di Yu, Paetra Brailsford, Maria Choi-Ali, Jonathan T Feng, Sixuan Li, Yining Zhu and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Jinghan Lin *Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.ORCID http://orcid.org/0009-0002-1475-1895
Yizong Hu *Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA. yizonghu@mit.edu.ORCID http://orcid.org/0000-0003-3983-5104
Turash H PialDepartment of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-6038-7900
Kailei D GoodierInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.ORCID http://orcid.org/0009-0008-2397-2079
Di YuInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.
Paetra BrailsfordBiogen Inc., Cambridge, MA, USA.
Maria Choi-AliBiogen Inc., Cambridge, MA, USA.
Jonathan T FengInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.ORCID http://orcid.org/0009-0003-4902-7132
Sixuan LiInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-0116-8812
Yining ZhuInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-7178-0097
Jingyao MaInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.
Leonardo ChengInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-9214-8533
Xiaoya LuInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.
Nicole KorinetzDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
Marine GuiseSartorius Polyplus, Illkirch-Graffenstaden, France.
Tza-Huei Jeff WangInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-3540-9354
Tine CurkInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-2167-5336
Hai-Quan MaoInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA. hmao@jhu.edu.ORCID http://orcid.org/0000-0002-4262-9988

Funding

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
NCI NIH HHS R01 CA281143U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA281143
6 · The paper itself

Abstract

Scalable, cost-effective manufacturing remains a major barrier to the clinical translation of viral vector-mediated gene therapies. The widely used transfection method for producing adeno-associated virus (AAVs) and lentivirus uses plasmid DNA (pDNA)/polyethyleneimine (PEI) particles loaded with multiple plasmids; however, these particles must be prepared at low concentrations and used immediately, limiting scalability and reproducibility. Here we show a kinetic-gating strategy in which transient binding of trivalent citrate ions slows complexation, modulating charge-neutralization kinetics and delaying particle nucleation, enabling the formation of stable, highly concentrated pDNA/PEI particles. By incorporating citrate, we prevent aggregation and achieve uniform assembly at high concentrations, enabling a ten-fold increase in DNA concentration (to 0.2 mg/mL) and reduced dosing volumes. The method is robust across mixing conditions, compatible with standard manufacturing workflows, and maintains AAV production efficiency across scales. These results establish a simple and generalizable approach to control polyelectrolyte assembly kinetics, improving the scalability and reliability of viral vector production.

Indexed as

DNAPlasmidsPolyethyleneimineCitric AcidDependovirusGenetic VectorsHumansIonsKineticsTransfectionCitric AcidDNAIonsPolyethyleneimine

Identifiers

PMID42230627
PMCPMC13392119

What OpenQuestion holds

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LicenceCC BY
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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.