Catheter-mediated pulmonary vascular gene transfer and expression

Area of Science:

• Pulmonary Medicine
• Gene Therapy
• Vascular Biology

Background:

• Pulmonary diseases require effective treatments.
• In vivo gene expression in the lungs can facilitate study and treatment of pulmonary diseases.

Purpose of the Study:

• To evaluate the feasibility of gene transfer to the pulmonary vasculature.
• To assess gene expression and safety following gene delivery to the lungs.

Main Methods:

• Cationic liposomes and adenoviral vectors encoding human placental alkaline phosphatase (hpAP) gene were delivered into the pulmonary artery of pigs via right heart catheterization.
• Pulmonary tissue was analyzed for gene transfer and expression at various time points (20 minutes to 28 days).
• Histological examination and biochemical analysis were performed to assess safety and off-target effects.

Main Results:

• Gene transfer and mRNA expression were demonstrated in lung tissue 5 days after delivery with both vectors.
• Recombinant alkaline phosphatase protein was found in the vasculature and alveolar septa, but not bronchi.
• Gene expression peaked at 5 days, diminished by 14 days, and was absent by 28 days.
• No major adverse effects or histological changes were observed in the lungs or other organs.

Conclusions:

• Intravascular gene delivery to the lung results in recombinant gene expression in the vasculature and alveoli.
• This approach provides a potential model for studying pulmonary vascular diseases like pulmonary fibrosis and thrombosis.
• The gene transfer methods evaluated were found to be safe in the short term.