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Efficient gene delivery to myocardium with ultrasound targeted microbubble destruction and polyethylenimine

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Summary

The aim of present study was to evaluate the feasibility and efficiency of enhanced green fluorescent protein (EGFP) gene delivery to myocardium in vivo by ultrasound targeted microbubble destruction (UTMD) and polyethylenimine (PEI). SonoVue/DNA and PEI/DNA/SonoVue complexes were prepared. Gel electrophoresis analysis was performed to determine the structural integrity of plasmid DNA or PEI/DNA after UTMD. Solutions of plasmid DNA, SonoVue/DNA, PEI/DNA complexes or PEI/DNA/SonoVue complexes were respectively transduced into BALB/c mice hearts by means of transthoracic ultrasound irradiation. Mice undergoing PBS injection, plasmid injection or PEI/DNA complexes injection without ultrasound irradiation served as controls. Gene expression in myocardium was detected 4 days after treatment. Cryosections and histological examinations were conducted. Electrophoresis gel assay showed no damage to DNA or PEI/DNA complexes after UTMD. When the heart was not exposed to ultrasound, the expression of EGFP was observed in the subendocardial myocardium obviously. The strongest expression was detected in the anterior wall of the left ventricle when the heart was exposed to ultrasound alone. Injection of PEI/DNA complexes and UTMD resulted in the highest transfection efficiency and the distributional difference of EGFP was not obvious. No tissue damage was seen histologically. In conclusion, a combination of UTMD and PEI was highly effective in transfecting mice hearts without causing any apparently adverse effect. It provides an alternative to current clinical gene therapy and opens a new concept of non-viral gene delivery for the treatment of cardiac disease.

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Authors and Affiliations

  1. Department of Ultrasonography, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China

    Zhiyi Chen  (陈智毅), Mingxing Xie  (谢明星), Xinfang Wang  (王新房), Qing Lv  (吕 清) & Shangwei Ding  (丁尚伟)

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  1. Zhiyi Chen  (陈智毅)
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  2. Mingxing Xie  (谢明星)
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  3. Xinfang Wang  (王新房)
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  4. Qing Lv  (吕 清)
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  5. Shangwei Ding  (丁尚伟)
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Additional information

The project was supported by a grant from the National Natural Sciences Foundation of China (No. 30670548).

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Chen, Z., Xie, M., Wang, X. et al. Efficient gene delivery to myocardium with ultrasound targeted microbubble destruction and polyethylenimine. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 28, 613–617 (2008). https://doi.org/10.1007/s11596-008-0528-4

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  • DOI: https://doi.org/10.1007/s11596-008-0528-4

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