Evidence map›Paper›PMID 19752373›Full record

ArticleCirculation2009

Novel minicircle vector for gene therapy in murine myocardial infarction.

Mei Huang, ZhiYing Chen, Shijun Hu, Fangjun Jia, Zongjin Li, Grant Hoyt, Robert C Robbins, Mark A Kay, Joseph C Wu

Abstract read
In one paragraph

Article in Circulation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
4.6field-weighted citation impact, top 5% 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

59 citing papers in PubMed, 101 citations in OpenAlex.

  1. Article
  2. Precision therapeutic tRNA rescue of nonsense mutation R166X inJournal of precision medicine (Amsterdam, Netherlands) · 2025
    Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Minicircle Delivery to the Neural Retina as a Gene Therapy Approach.International journal of molecular sciences · 2022
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Pathophysiology of Aortic Aneurysms: Insights from Animal Studies.Cardiology and cardiovascular medicine · 2020
    Article
  15. Article
  16. Article
  17. The Current Status of COVID-19 Vaccines.Frontiers in genome editing · 2020
    Review
  18. Article
  19. Article
  20. 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

9 authors at 2 institutions in 2 countries.

Mei HuangDepartment of Radiology, Stanford University School of Medicine, CA 94305-5344, USA.
ZhiYing Chen
Shijun Hu
Fangjun Jia
Zongjin Li
Grant Hoyt
Robert C Robbins
Mark A Kay
Joseph C Wu
Stanford University · USInstitute of Ophthalmology · MX

Funding

Molecular Imaging of Targeted Cardiac Gene TherapyR01HL093172 · NHLBI · STANFORD UNIVERSITY · PI WU, JOSEPH C. · 2009 to 2015
$2.7M
09: Inducing Pluripotency with MiRNAs: New Paradigm Shif in Cell ReprogrammingDP2OD004437 · OD · STANFORD UNIVERSITY · PI WU, JOSEPH C. · 2008 to 2008
$2.4M
Nanostructuring and Molecular Imaging of Engineered Cardiovascular TissuesR33HL089027 · NHLBI · STANFORD UNIVERSITY · PI WU, JOSEPH C. · 2009 to 2011
$2.3M
Nanostructuring and Molecular Imaging of Engineered Cardiovascular TissuesR21HL089027 · NHLBI · STANFORD UNIVERSITY · PI WU, JOSEPH C. · 2007 to 2008
$777k
NHLBI NIH HHS HL093172NHLBI NIH HHS R01 HL093172NHLBI NIH HHS R21 HL089027NHLBI NIH HHS R33 HL089027NIH HHS DP2 OD004437
6 · The paper itself

Abstract

backgroundConventional plasmids for gene therapy produce low-level and short-term gene expression. In this study, we develop a novel nonviral vector that robustly and persistently expresses the hypoxia-inducible factor-1 alpha (HIF-1alpha) therapeutic gene in the heart, leading to functional benefits after myocardial infarction. METHODS AND

resultsWe first created minicircles (MC) carrying double-fusion reporter gene consisting of firefly luciferase and enhanced green fluorescent protein (Fluc-eGFP) for noninvasive measurement of transfection efficiency. Mouse C2C12 myoblasts and normal FVB/N mice were used for in vitro and in vivo confirmation, respectively. Bioluminescence imaging showed stable MC gene expression in the heart for >12 weeks and the activity level was 5.6+/-1.2-fold stronger than regular plasmid at day 4 (P<0.01). Next, we created MC carrying HIF-1alpha (MC-HIF-1alpha) therapeutic gene for treatment of myocardial infarction. Adult FVB/N mice underwent left anterior descending ligation and were injected intramyocardially with: (1) MC-HIF-1alpha; (2) regular plasmid carrying HIF-1alpha (PL-HIF-1alpha) as positive control; and (3) PBS as negative control (n=10/group). Echocardiographic study showed a significantly greater improvement of left ventricular ejection fraction in the MC group (51.3%+/-3.6%) compared to regular plasmid group (42.3%+/-4.1%) and saline group (30.5%+/-2.8%) at week 4 (P<0.05 for both). Histology demonstrated increased neoangiogenesis in both treatment groups. Finally, Western blot showed MC express >50% higher HIF-1alpha level than regular plasmid.

conclusionsTaken together, this is the first study to our knowledge to demonstrate that MC can significantly improve transfection efficiency, duration of transgene expression, and cardiac contractility. Given the serious drawbacks associated with most viral vectors, we believe this novel nonviral vector can be of great value for cardiac gene therapy protocols.

Indexed as

Genetic VectorsAnimalsCells, CulturedDNA, SuperhelicalEscherichia coliFemaleGenetic TherapyHypoxia-Inducible Factor 1, alpha SubunitMiceMyocardial InfarctionPlasmidsDNA, SuperhelicalHif1a protein, mouseHypoxia-Inducible Factor 1, alpha Subunit

Identifiers

PMID19752373
PMCPMC3163107
OpenAlexW2046014353

What OpenQuestion holds

Textmetadata
LicenceTDM
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.