Evidence map›Paper›PMID 21829177›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2011

N-acetylcysteine enhances cystic fibrosis sputum penetration and airway gene transfer by highly compacted DNA nanoparticles.

Jung Soo Suk, Nicholas J Boylan, Kanika Trehan, Benjamin C Tang, Craig S Schneider, Jung-Ming G Lin, Michael P Boyle, Pamela L Zeitlin, Samuel K Lai, Mark J Cooper and 1 more

Open access · hybridAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
5.2field-weighted citation impact, top 4% 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

48 citing papers in PubMed, 95 citations in OpenAlex.

  1. Trial
  2. Review
  3. Review
  4. Article
  5. Nanoparticle-Based Pulmonary Immune Engineering.Annual review of chemical and biomolecular engineering · 2025
    Review
  6. Review
  7. Review
  8. Article
  9. Article
  10. Impact of mucus modulation byInternational journal of pharmaceutics: X · 2023
    Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Current views in chronic obstructive pulmonary disease pathogenesis and management.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2021
    Review
  16. Review
  17. Review
  18. Review
  19. Article
  20. Nanoparticle Delivery Systems with Cell-Specific Targeting for Pulmonary Diseases.American journal of respiratory cell and molecular biology · 2021
    Review
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

11 authors at 2 institutions in 1 country.

Jung Soo SukDepartment of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
Nicholas J Boylan
Kanika Trehan
Benjamin C Tang
Craig S Schneider
Jung-Ming G Lin
Michael P Boyle
Pamela L Zeitlin
Samuel K Lai
Mark J Cooper
Justin Hanes
Johns Hopkins University · USCopernicus Therapeutics (United States) · US

Funding

Institute for Clinical and Translational Research (UL1)UL1RR025005 · NCRR · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2007 to 2011
$75.8M
Vector CoreP01HL051811 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI GUGGINO, WILLIAM B. · 1993 to 2013
$20.2M
New Gene Vectors for Cystic Fibrosis (CF): Extra- & Intracellular BarriersR01EB003558 · NIBIB · JOHNS HOPKINS UNIVERSITY · PI HANES, JUSTIN S. · 2007 to 2010
$1.4M
NCRR NIH HHS UL1 RR 025005NCRR NIH HHS UL1 RR025005NHLBI NIH HHS P01 HL051811NHLBI NIH HHS P01 HL51811NIBIB NIH HHS 1R01 EB003558NIBIB NIH HHS R01 EB003558
6 · The paper itself

Abstract

For effective airway gene therapy of cystic fibrosis (CF), inhaled gene carriers must first penetrate the hyperviscoelastic sputum covering the epithelium. Whether clinically studied gene carriers can penetrate CF sputum remains unknown. Here, we measured the diffusion of a clinically tested nonviral gene carrier, composed of poly-l-lysine conjugated with a 10 kDa polyethylene glycol segment (CK(30)PEG(10k)). We found that CK(30)PEG(10k)/DNA nanoparticles were trapped in CF sputum. To improve gene carrier diffusion across sputum, we tested adjuvant regimens consisting of N-acetylcysteine (NAC), recombinant human DNase (rhDNase) or NAC together with rhDNase. While rhDNase alone did not enhance gene carrier diffusion, NAC and NAC + rhDNase increased average effective diffusivities by 6-fold and 13-fold, respectively, leading to markedly greater fractions of gene carriers that may penetrate sputum layers. We further tested the adjuvant effects of NAC in the airways of mice with Pseudomonas aeruginosa lipopolysaccharide (LPS)-induced mucus hypersecretion. Intranasal dosing of NAC prior to CK(30)PEG(10k)/DNA nanoparticles enhanced gene expression by up to ~12-fold compared to saline control, reaching levels observed in the lungs of mice without LPS challenge. Our findings suggest that a promising synthetic nanoparticle gene carrier may transfer genes substantially more effectively to lungs of CF patients if administered following adjuvant mucolytic therapy with NAC or NAC + rhDNase.

Indexed as

AcetylcysteineAdultAnimalsBiopolymersCystic FibrosisDiffusionDNAExpectorantsFemaleGenetic TherapyHumansMaleMiceMice, Inbred C57BLMucinsNanoparticlesAcetylcysteineBiopolymersDNAExpectorantsMucinsPolyethylene GlycolsPolylysine

Identifiers

PMID21829177
PMCPMC3222526
OpenAlexW2091215591

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.