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Updated: Sep 19, 2025
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Gene Transfer for Ischemic Heart Failure in a Preclinical Model
Published on: May 15, 2011
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Cardiac-Targeted AAV5-S100A1 Gene Therapy Protects Against Adverse Remodeling and Contractile Dysfunction in
Dorothea Kehr1,2,3, Janek Salatzki2, Birgit Seger1,2
1Division of Molecular and Translational Cardiology (D.K., B.S., K.V., J.B., A.J., M.B., J. Ritterhoff, P.M.), University Hospital Heidelberg, Germany.
Circulation. Heart Failure
|June 19, 2025
Summary
Adeno-associated virus 5 (AAV5) effectively delivers genes to healthy and dysfunctional hearts in a human-sized model. This gene therapy shows promise for treating heart failure with long-term safety and efficacy.
Area of Science:
- Cardiovascular Research
- Gene Therapy
- Viral Vector Technology
Background:
- Translational study guided by long-term safety data of adeno-associated virus 5 (AAV5) in humans.
- Investigated AAV5 for gene delivery to healthy and dysfunctional human-sized hearts.
Purpose of the Study:
- To assess AAV5's efficacy in gene delivery and therapeutic potential in cardiac dysfunction.
- To evaluate AAV5 in a clinically relevant administration mode and dosage.
Main Methods:
- Percutaneous catheter-based retrograde intravenous vector delivery in pigs.
- Generation of postmyocardial infarction (MI) porcine and murine models.
- Assessment of cardiac function (ejection fraction, MI size) and safety (clinical chemistry, ECG).
Main Results:
- AAV5 achieved broad, homogenous transduction of healthy pig hearts without toxicity.
- AAV5 demonstrated superior distribution compared to AAV9 and AAV6.
- AAV5 carrying the hS100A1 gene prevented MI extension and improved cardiac function in post-MI pigs.
Conclusions:
- AAV5 provides a clinically relevant proof of concept for transducing human-sized hearts.
- AAV5's safety profile, producibility, and low human immunity suggest its potential for treating chronic heart failure.
