Safety and bioactivity of intracoronary delivery of naked plasmid DNA encoding human atrial natriuretic factor.

ABSTRACT

AIM: To evaluate the safety and bioactivity of catheter-mediated intracoronary gene delivery of naked plasmid DNA encoding human atrial natriuretic factor (hANF). METHODS: hANF gene delivery was performed in 12 canines. For each canine, 4 mg of reconstructed naked plasmid DNA encoding hANF (pCR3*hANF, n=6) or pCR3 (n=6, control) in 2 mL normal saline was injected into left coronary artery via a coronary angiographic catheter. The expression of hANF mRNA in left ventricular myocardium, liver, lung, and kidney was identified by reverse transcription polymerase chain reaction and Southern blot analysis 40 d after gene delivery. Plasma ANF levels were determined by radioimmunoassay. RESULTS: The naked pCR3*hANF caused significant expression of hANF mRNA in ventricular myocardium (P <0.01). No hANF mRNA was detected in distal tissues, including liver, lung, and kidney (P >0.05). ANF levels were significantly higher in pCR3*hANF group than those in control group. CONCLUSION: These facts firstly demonstrate that intracoronary delivery of naked pCR3*hANF is probably a safe and feasible method for gene delivery by which hANF gene can be expressed in ventricular myocardium effectively.