Evidence map›Paper›PMID 35879315›Full record

ArticleNature communications2022

Multi-step screening of DNA/lipid nanoparticles and co-delivery with siRNA to enhance and prolong gene expression.

Yining Zhu, Ruochen Shen, Ivan Vuong, Rebekah A Reynolds, Melanie J Shears, Zhi-Cheng Yao, Yizong Hu, Won June Cho, Jiayuan Kong, Sashank K Reddy and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
9.9field-weighted citation impact, top 1% of its field
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

76 citing papers in PubMed, 122 citations in OpenAlex.

  1. Article
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  9. NNature · 2026
    Article
  10. Article
  11. Review
  12. Article
  13. Decoding Undesirable Inflammatory Responses of Nucleic Acid-Delivering Lipid Nanoparticles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review

16 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

12 authors at 2 institutions in 1 country.

Yining ZhuDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ruochen ShenDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0001-9967-4758
Ivan VuongDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Rebekah A ReynoldsDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
Melanie J ShearsDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.ORCID 0000-0002-8226-4354
Zhi-Cheng YaoInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.
Yizong HuDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Won June ChoInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.
Jiayuan KongDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Sashank K ReddyDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Sean C MurphyDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA. murphysc@uw.edu.ORCID 0000-0002-2048-0131
Hai-Quan MaoDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA. hmao@jhu.edu.ORCID 0000-0002-4262-9988
Johns Hopkins University · USUniversity of Washington · US

Funding

Development of an oral liver-targeted prime-and-trap malaria vaccineU01AI155313 · NIAID · UNIVERSITY OF WASHINGTON · PI MURPHY, SEAN C · 2021 to 2025
$4.1M
NIAID NIH HHS U01 AI155313
6 · The paper itself

Abstract

Lipid nanoparticles hold great potential as an effective non-viral vector for nucleic acid-based gene therapy. Plasmid DNA delivery can result in extended transgene expression compared to mRNA-based technologies, yet there is a lack of systematic investigation into lipid nanoparticle compositions for plasmid DNA delivery. Here, we report a multi-step screening platform to identify optimized plasmid DNA lipid nanoparticles for liver-targeted transgene expression. To achieve this, we analyze the role of different helper lipids and component ratios in plasmid DNA lipid nanoparticle-mediated gene delivery in vitro and in vivo. Compared to mRNA LNPs and in vivo-jetPEI/DNA nanoparticles, the identified plasmid DNA lipid nanoparticles successfully deliver transgenes and mediate prolonged expression in the liver following intravenous administration in mice. By addressing different physiological barriers in a stepwise manner, this screening platform can efficiently down select effective lipid nanoparticle candidates from a lipid nanoparticle library of over 1000 formulations. In addition, we substantially extend the duration of plasmid DNA nanoparticle-mediated transgene expression using a DNA/siRNA co-delivery approach that targets transcription factors regulating inflammatory response pathways. This lipid nanoparticle-based co-delivery strategy further highlights the unique advantages of an extended transgene expression profile using plasmid DNA delivery and offers new opportunities for DNA-based gene medicine applications.

Indexed as

LipidsNanoparticlesAnimalsDNAGene ExpressionLiposomesMiceRNA, MessengerRNA, Small InterferingDNALipid NanoparticlesLipidsLiposomesRNA, MessengerRNA, Small Interfering

Identifiers

PMID35879315
PMCPMC9310361
OpenAlexW4287378014

What OpenQuestion holds

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LicenceCC BY
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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 OpenQuestion graph.