Evidence map›Paper›PMID 26124127›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

Highly compacted biodegradable DNA nanoparticles capable of overcoming the mucus barrier for inhaled lung gene therapy.

Panagiotis Mastorakos, Adriana L da Silva, Jane Chisholm, Eric Song, Won Kyu Choi, Michael P Boyle, Marcelo M Morales, Justin Hanes, Jung Soo Suk

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.

0numbers the graph read from it
0cells of the map it votes in
115citing 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

115 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Review
  6. Review
  7. Review
  8. PBAE-PEG-based lipid nanoparticles for lung cell-specific gene delivery.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Biopolymeric Inhalable Dry Powders for Pulmonary Drug Delivery.Pharmaceuticals (Basel, Switzerland) · 2024
    Review
  15. Highly branched poly β-amino ester/CpG-depletedMolecular therapy. Methods & clinical development · 2024
    Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Review

55 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

9 authors.

Panagiotis MastorakosCenter for Nanomedicine, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21297;
Adriana L da SilvaLaboratory of Cellular and Molecular Physiology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941902, Brazil;
Jane ChisholmCenter for Nanomedicine, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218;
Eric SongCenter for Nanomedicine, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231; Center for Biotechnology Education, Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, MD 21218;
Won Kyu ChoiCenter for Nanomedicine, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218;
Michael P BoyleAdult Cystic Fibrosis Program, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Marcelo M MoralesLaboratory of Cellular and Molecular Physiology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941902, Brazil;
Justin HanesCenter for Nanomedicine, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21297; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218; hanes@jhmi.edu jsuk@jhmi.edu.
Jung Soo SukCenter for Nanomedicine, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21297; hanes@jhmi.edu jsuk@jhmi.edu.

Funding

Vector CoreP01HL051811 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI GUGGINO, WILLIAM B. · 1993 to 2013
$20.2M
Biodegradable Mucus Penetrating DNA Nanoparticle for Gene Therapy of CFR01HL127413 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI HANES, JUSTIN S., SUK, JUNG SOO · 2015 to 2018
$1.6M
NHLBI NIH HHS P01 HL051811NHLBI NIH HHS P01 HL51811NHLBI NIH HHS R01 HL127413
6 · The paper itself

Abstract

Gene therapy has emerged as an alternative for the treatment of diseases refractory to conventional therapeutics. Synthetic nanoparticle-based gene delivery systems offer highly tunable platforms for the delivery of therapeutic genes. However, the inability to achieve sustained, high-level transgene expression in vivo presents a significant hurdle. The respiratory system, although readily accessible, remains a challenging target, as effective gene therapy mandates colloidal stability in physiological fluids and the ability to overcome biological barriers found in the lung. We formulated highly stable DNA nanoparticles based on state-of-the-art biodegradable polymers, poly(β-amino esters) (PBAEs), possessing a dense corona of polyethylene glycol. We found that these nanoparticles efficiently penetrated the nanoporous and highly adhesive human mucus gel layer that constitutes a primary barrier to reaching the underlying epithelium. We also discovered that these PBAE-based mucus-penetrating DNA nanoparticles (PBAE-MPPs) provided uniform and high-level transgene expression throughout the mouse lungs, superior to several gold standard gene delivery systems. PBAE-MPPs achieved robust transgene expression over at least 4 mo following a single administration, and their transfection efficiency was not attenuated by repeated administrations, underscoring their clinical relevance. Importantly, PBAE-MPPs demonstrated a favorable safety profile with no signs of toxicity following intratracheal administration.

Indexed as

Genetic TherapyMucusAdministration, InhalationAnimalsCystic FibrosisDNAMiceNanoparticlesDNAbiodegradable polymerlung gene therapymucus-penetrating particlesnanotechnologynonviral gene delivery

Identifiers

PMID26124127
PMCPMC4507234

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.