New efficient catheter-based system for myocardial gene delivery.

Area of Science:

• Cardiovascular Research
• Gene Therapy
• Medical Imaging

Background:

• Cardiac gene therapy holds promise for treating heart failure.
• Current methods for efficient cardiac gene delivery often require invasive open-chest surgery.
• Developing minimally invasive techniques is crucial for advancing cardiac gene therapy.

Purpose of the Study:

• To test a novel hypothesis for maximizing cardiac vector delivery using echo contrast microbubbles.
• To investigate a catheter-based approach combining microbubbles, aortic root injection, and pharmacologic vasodilation.
• To achieve efficient and homogeneous cardiac gene delivery in a closed-chest model.

Main Methods:

• Adenovirus encoding a reporter gene was incubated with albumin-coated perfluorocarbon microbubbles.
• Vectors were infused into the aortic root of rats with transient balloon occlusion.
• Acetylcholine (ACh) was used to prolong diastole and induce vasodilation.
• Ultrasound was employed for imaging and microbubble disruption.

Main Results:

• The combined approach (aortic occlusion with ACh) increased myocardial gene expression by over 2.5-fold compared to microbubbles alone.
• Significant gene expression was achieved with the vector alone, but less than the combined method.
• The novel delivery system demonstrated substantial and statistically significant myocardial gene uptake.

Conclusions:

• A catheter-based adenoviral delivery system using echo contrast and optimized coronary perfusion enhances gene delivery.
• This innovative method enables efficient percutaneous gene delivery in a closed-chest setting.
• The findings support a less invasive strategy for cardiac gene therapy.