Myocardial gene delivery using molecular cardiac surgery with recombinant adeno-associated virus vectors in vivo
Open accessAbstract
We use a novel technique that allows for closed recirculation of vector genomes in the cardiac circulation using cardiopulmonary bypass, referred to here as molecular cardiac surgery with recirculating delivery (MCARD). We demonstrate that this platform technology is highly efficient in isolating the heart from the systemic circulation in vivo. Using MCARD, we compare the relative efficacy of single-stranded (ss) adeno-associated virus (AAV)6, ssAAV9 and self-complimentary (sc)AAV6-encoding enhanced green fluorescent protein, driven by the constitutive cytomegalovirus promoter to transduce the ovine myocardium in situ. MCARD allows for the unprecedented delivery of up to 48 green fluorescent protein genome copies per cell globally in the sheep left ventricular (LV) myocardium. We demonstrate that scAAV6-mediated MCARD delivery results in global, cardiac-specific LV gene expression in the ovine heart and provides for considerably more robust and cardiac-specific gene delivery than other available delivery techniques such as intramuscular injection or intracoronary injection; thus, representing a potential, clinically translatable platform for heart failure gene therapy.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Transduction of sheep myocardium with AAV vectors such as AAV-6 and AAV-2/1 has been successfully performed with techniques such as coronary infusion coupled with brief coronary and venous blockage and re-circulating systems.
“Transduction of sheep myocardium with AAV vectors (such as AAV-6 and AAV-2/1) have been successfully performed with techniques such as coronary infusion coupled with brief coronary and venous blockage (Beeri, et al., 2010) and re-circulating systems (Byrne, et al., 2008; J. D. White, et al., 2011) which target the myocardium directly and increase exposure time.”
From Small and large animal models in cardiac contraction research: advantages and disadvantages (2014) · cites this paper as J. D. White, et al., 2011
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 23 · Cited by 73
- Authors
- White, J. D., Thesier, D. M., Swain, J. B. D., Katz, M. G., Tomasulo, C., Henderson, A., Wang, L., Yarnall, C., Fargnoli, A., Sumaroka, M., Isidro, A., Petrov, M., Holt, D., Nolen-Walston, R., Koch, W. J., Stedman, H. H., Rabinowitz, J., & Bridges, C. R.
- Affiliations
- University of Pennsylvania (US)
- Thomas Jefferson University (US)
- Corresponding author
- Bridges, C R
- Venue
- Gene Therapy
- Published
- 2011-01-13
- Volume
- 18
- Issue
- 6
- Pages
- 546-552
- ISSN
- 0969-7128 (ISSN-L)
- 1476-5462
- PMC
- PMC3690495
- OpenAlex
- W1979195698
- Cited by
- 73
- References
- 23
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 2 · 2023: 8 · 2022: 3 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 7 · 2015: 8 · 2014: 5 · 2013: 13 · 2012: 11
- FWCI
- 7.08
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Gene Therapy (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (1-R01-HL083078-01A2, R01HL083078)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK047757)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Engineering › Biomedical Engineering › Mechanical Circulatory Support Devices
- Keywords
- cardiopulmonary bypass, adeno-associated virus vectors, enhanced green fluorescent protein, left ventricle, cardiac-specific gene expression
- MeSH terms
- Dependovirus, Animals, Cardiopulmonary Bypass, Cytomegalovirus, Genetic Vectors, Cardiac Surgical Procedures, Myocardium, Sheep, Genetic Therapy, Gene Transfer Techniques, Green Fluorescent Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
