Ultrasound-mediated transfection of canine myocardium by intravenous administration of cationic microbubble-linked plasmid DNA.
We tested the hypothesis that targeted disruption of cationic microbubble-linked plasmid DNA, using diagnostic ultrasound, may aid transfection of large animal myocardium. Plasmid DNA encoding for CAT (pCAT, chloramphenicol acetyltransferase) was bound to a novel cationic microbubble containing MRX-225 for intravenous administration, and 16 dogs in 4 groups variously received this conjugate or plasmid only, or were exposed to ultrasound. Histochemical staining and enzyme-linked immunosorbent assay analysis showed CAT activity in the myocardium of only those animals that received microbubble-linked DNA and were exposed to ultrasound. Thus, disruption of cationic-linked, low-dose plasmid systems by diagnostic ultrasound may facilitate transfection of large animal hearts.
Vannan
Mani
M
Department of Internal Medicine, Division of Cardiology, University of Michigan Health System, Ann Arbor, Michigan, USA. mav25@drexel.edu
McCreery
Thomas
T
Li
Peng
P
Han
Zhenguo
Z
Unger
Evan
E
Kuersten
Bettina
B
Nabel
Elizabeth
E
Rajagopalan
Sanjay
S
D026923:Amino Acid Transport Systems, Basic; D000704:Analysis of Variance; D000818:Animals; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004247:DNA / Q000008:administration & dosage*; D004285:Dogs; D004452:Echocardiography / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D007275:Injections, Intravenous; D008297:Male; D008863:Microspheres; D009206:Myocardium / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D014162:Transfection / Q000379:methods*
D026923:Amino Acid Transport Systems, Basic; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase