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Ann Thorac Surg 2000;70:1332-1337
© 2000 The Society of Thoracic Surgeons

Original articles: cardiovascular

In vivo gene gun–mediated transduction into rat heart with Epstein-Barr virus-based episomal vectors

Kazuhiko Nishizaki, MDa,c,d, Osam Mazda, MD, PhDa,c,d, Yoshiko Dohi, PhDb,c,d, Tetsuji Kawata, MDa,c,d, Kazumi Mizuguchi, MDa,c,d, Soichiro Kitamura, MDa,c,d, Shigeki Taniguchi, MDa,c,d

a Department of Surgery III, Nara Medical University, Nara, Japan
b Department of Public Health, Nara Medical University, Nara, Japan
c Department of Microbiology, Kyoto Prefectural University of Medicine, Kyoto, Japan
d Division of Cardiovascular Surgery, National Cardiovascular Center, Osaka, Japan

Address reprint requests to Dr Nishizaki, Department of Surgery III, Nara Medical University, Kashihara, Nara 634–8522, Japan
e-mail: nszk{at}naramed-u.ac.jp

Background. Gene guns have been used to transfer genes into various organs, but there has been no report of successful gene gun–mediated gene transfer into the heart. In this study, we assessed the possibility of gene therapy using a gene gun and an episomal plasmid vector.

Methods. Gene transfer was performed using two sizes of gold particles and two plasmids (an episomal vector and a conventional plasmid vector). From the first to eighth week after the bombardment, rats were sacrificed. The excised hearts were subjected to X-gal staining and histologic examination. To ensure that plasmid was not distributed to organs other than the heart, the presence of the ß-gal sequence was examined by polymerase chain reaction analyses.

Results. Gene expression persisted for 6 weeks. The episomal vector apparently contributed to long-lasting expression. Infiltration of monocytes or leukocytes was very faint. The ß-gal DNA was detected in bombarded hearts but not other organs.

Conclusions. Gene gun–mediated transfer of the episomal vector into beating heart may provide a simple, efficient, and useful strategy for gene therapy.




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