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ISSN
1672-9145
Acta Biochim Biophys Sin
2004, 36(12): 824–831
CN 31-1940/Q
Ultrasound/Microbubble Enhances Foreign Gene Expression in ECV304
Cells and Murine Myocardium
Dongping GUO, Xiaoyu LI, Ping SUN, Zhiguang WANG, Xiuying CHEN, Qi
CHEN, Leming FAN*, Bin ZHANG1,
Lizheng SHAO1, and Xiaorong LI1
Atherosclerosis Research Center, Nanjing Medical University, Nanjing
210029, China;
1Cardiovascular
Division, Wuxi No. 1 Hospital, Wuxi 214002, China
Abstract Although viral vectors
are efficient systems to transfer foreign genes into cells or target tissues,
safety issues remain in relation to human gene therapy. Microbubbles currently
used as ultrasound contrast agents have been applied in transfection of genes.
This study was designed to test the transfection efficiency and the expression
of exogenous gene mediated by ultrasound irradiation enhanced air filled albumin
microbubbles in ECV304 cell line in vitro and the heart of the mouse
in vivo. Air filled microbubbles (2.0–4.0 mm in diameter)
were created by sonicating the mixture of human albumin, glucose, mannitol
and special additive that was designed for stabilization. Plasmid DNA loading
the reporter genes was gently mixed with microbubbles. The mixture
of plasmid DNA and microbubbles was administrated to cultured ECV304 cells
and BALB/c mice (tail vein injection) under different ultrasound/microbubble
conditions, and then the transfection and expression efficiency were examined.
The results both in vivo and in vitro demonstrated that microbubble
with ultrasound irradiation could significantly elevate the exogenous gene
expression as compared with microbubble or ultrasound only. Overall, the present
study showed that the ultrasound-target microbubble destruction method enhanced
the exogenous gene expression in vivo and in vitro, and provided
a gene therapy way not only efficient but also easy to be manipulated and
carried out in clinical.
Key words microbubble; ultrasound;
transfection; gene therapy
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Received: September 29, 2004 Accepted: November 15,
2004
This study was supported by the grants from the National Natural Science
Foundation of China (No. 30370659) and the Natural Science Fund of Jiangsu
Province of China (No. BK2002028)
*Corresponding author: Tel, 86-25-86862888; Fax, 86-25-86508960;
E-mail, [email protected]