Cardiac gene delivery with cardiopulmonary bypass

Area of Science:

• Cardiovascular Research
• Gene Therapy
• Molecular Cardiology

Background:

• Current cardiac gene therapy faces challenges with limited myocardial expression and risks of extracardiac spread.
• Cardiac surgery offers a potential window for enhanced and cardiac-specific gene delivery.

Purpose of the Study:

• To evaluate the efficacy and cardiac selectivity of adenoviral vector delivery during cardiopulmonary bypass and cardioplegic arrest.
• To assess myocardial transgene expression and potential off-target effects in a clinically relevant model.

Main Methods:

• Neonatal piglets underwent median sternotomy, cardiopulmonary bypass, and cardioplegic arrest.
• Adenoviral vectors encoding beta-galactosidase or human beta(2)-adrenergic receptor were delivered via the cardioplegia cannula.
• Gene expression was analyzed in heart, lung, and liver tissues after one week.

Main Results:

• Transmural myocardial expression of beta-galactosidase was observed.
• Delivery of the human beta(2)-adrenergic receptor significantly increased receptor density in the left ventricle (396% of control).
• No transgene expression was detected in liver or lung tissues, and no cardiac inflammation was evident.

Conclusions:

• Intracoronary delivery of adenoviral vectors during cardiopulmonary bypass and cardioplegic arrest enables efficient myocardial uptake and expression.
• This technique suggests a promising strategy for achieving cardiac-selective gene delivery, minimizing off-target transgene expression.