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.
Keywords:
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.