Ultrasound-mediated transfection of canine myocardium by intravenous administration of cationic microbubble-linked plasmid DNA

• DOI: 10.1067/mje.2002.119913
• Publication Date: 2002-08-24T22:14:26Z
• Authors: Mani Vannan; Thomas McCreery; Peng Li; Zhenguo Han; Evan Unger; Bettina Kuersten; Elizabeth Nabel; Sanjay Rajagopalan
• Keywords: Chloramphenicol O-Acetyltransferase; Male; 0301 basic medicine; Analysis of Variance; Myocardium; Gene Expression; Enzyme-Linked Immunosorbent Assay; DNA; Transfection; Microspheres; 3. Good health; 03 medical and health sciences; Dogs; Echocardiography; Injections, Intravenous; Amino Acid Transport Systems, Basic; Animals; Female; Plasmids

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.