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


CONCLUSIONS
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.
Huang
Guo-Ming
GM
Department of Cardiology, 94th Hospital of PLA, Nanchang 330002, China. huangguoming@hotmail.com
Li
Geng-Shan
GS
Zhu
Gang-Yan
GY
Lai
Yi-Mu
YM
Zhang
Hong-Xiang
HX
Wang
Jing
J
Wang
Hong-Ru
HR
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D006328:Cardiac Catheterization; D003331:Coronary Vessels; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D004285:Dogs; D015316:Genetic Therapy / Q000379:methods; D009206:Myocardium / Q000378:metabolism*; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics
D012333:RNA, Messenger; D009320:Atrial Natriuretic Factor; D004247:DNA