Efficient catheter-mediated gene transfer into the heart using replication-defective adenovirus

Area of Science:

• Cardiovascular Research
• Gene Therapy
• Molecular Medicine

Background:

• Gene therapy holds potential for cardiovascular diseases.
• Previous in vivo cardiac gene transfer methods had low efficiency.
• Effective gene delivery to coronary vasculature and myocardium is challenging.

Purpose of the Study:

• To develop an efficient method for in vivo gene transfer to the heart.
• To evaluate catheter-mediated adenovirus infusion for cardiac gene expression.
• To assess the safety and duration of gene expression following intracoronary adenovirus delivery.

Main Methods:

• Replication-defective adenovirus was infused into the coronary arteries of rabbits.
• Gene expression levels were assessed in coronary arteries and myocardium.
• Tissue distribution of adenovirus DNA was analyzed using polymerase chain reaction (PCR).
• Safety was evaluated by monitoring for inflammatory responses and myocardial necrosis.

Main Results:

• Catheter-mediated intracoronary adenovirus infusion achieved high-level recombinant gene expression.
• Sustained gene expression was observed in coronary arteries and myocardium for at least 2 weeks.
• No significant inflammatory response or myocardial necrosis was detected.
• Adenovirus DNA was detected in multiple organs, including liver, kidneys, lungs, brain, and testes, 5 days post-infusion.

Conclusions:

• Percutaneous transluminal gene transfer (PTGT) using intracoronary adenovirus infusion is an efficient and novel method for cardiac gene delivery.
• This approach enables gene expression in both the coronary arterial wall and the myocardium.
• PTGT offers a relatively non-invasive strategy for treating cardiovascular diseases via gene therapy.