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Successful and optimized in vivo gene transfer to rabbit carotid artery mediated by electronic pulse

Gene Therapy volume 8, pages 1174–1179 (2001)Cite this article

Abstract

Several gene transfer methods, including viral or nonviral vehicles have been developed, however, efficacy, safety or handling continue to present problems. We developed a nonviral and plasmid-based method for arterial gene transfer by in vivo electronic pulse, using a newly designed T-shaped electrode. Using rabbit carotid arteries, we first optimized gene transfer efficiency, and firefly luciferase gene transfer via electronic pulse under 20 voltage (the pulse length: Pontime 20 ms, the pulse interval: Poff time 80 ms, number of pulse: 10 times) showed the highest gene expression. Exogenous gene expression was detectable for at least up to 14 days. Electroporation-mediated gene transfer of E. coli lacZ with nuclear localizing signal revealed successful gene transfer to luminal endothelial cells and to medial cells. Histological damage was recognized as the voltage was increased but neointima formation 4 weeks after gene transfer was not induced. In vivo electroporation-mediated arterial gene transfer is readily facilitated, is safe and may prove to be an alternative form of gene transfer to the vasculature.

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References

  1. Arnold TE, Gnatenko D, Bahou WF . In vivo gene transfer into rat arterial walls with novel adeno-associated virus vectors J Vasc Surg 1997 25: 347–355

    Article  CAS  Google Scholar 

  2. Plautz G, Nabel EG, Nabel GJ . Introduction of vascular smooth muscle cells expressing recombinant genes in vivo Circulation 1991 83: 578–583

    Article  CAS  Google Scholar 

  3. Lee SW et al. In vivo adenoviral vector-mediated gene transfer into balloon-injured rat carotid arteries Circ Res 1993 73: 797–807

    Article  CAS  Google Scholar 

  4. Channon KM et al. Acute host-mediated endothelial injury after adenoviral gene transfer in normal rabbit arteries: impact on transgene expression and endothelial function Circ Res 1998 82: 1349–1351

    Article  Google Scholar 

  5. Riessen R et al. Arterial gene transfer using pure DNA applied directly to a hydrogel-coated angioplasty balloon Hum Gene Ther 1993 4: 749–758

    Article  CAS  Google Scholar 

  6. Nabel EG, Plautz G, Nabel GJ . Site-specific gene expression in vivo by direct gene transfer into the arterial wall Science 1990 249: 1285–1288

    Article  CAS  Google Scholar 

  7. Baum C, Forster P, Hegewisch-Becker S, Harbers K . An optimized electroporation protocol applicable to a wide range of cell lines Biotechniques 1994 17: 1058–1062

    CAS  Google Scholar 

  8. Andreason GL, Evans GA . Optimization of electroporation for transfection of mammalian cell lines Anal Biochem 1989 180: 269–275

    Article  CAS  Google Scholar 

  9. Green NK et al. Transfection of cardiac muscle: effects of overexpression of c-myc and c-fos proto-oncogene proteins in primary cultures of neonatal rat cardiac myocytes Clin Sci 1997 92: 181–188

    Article  CAS  Google Scholar 

  10. Kotnis RA et al. Optimisation of gene transfer into vascular endothelial cells using electroporation Eur J Vasc Endovasc Surg 1995 9: 71–79

    Article  CAS  Google Scholar 

  11. Van Tendeloo VF et al. High-level transgene expression in primary human T lymphocytes and adult bone marrow CD34+ cells via electroporation-mediated gene delivery Gene Therapy 2000 7: 1431–1437

    Article  CAS  Google Scholar 

  12. Aihara H, Miyazaki J . Gene transfer into muscle by electroporation in vivo Nat Biotechnol 1998 16: 867–870

    Article  CAS  Google Scholar 

  13. Gehl J et al. In vivo electroporation of skeletal muscle: threshold, efficacy and relation to electric field distribution Biochim Biophys Acta 1999 1428: 233–240

    Article  CAS  Google Scholar 

  14. Muramatsu T, Mizutani Y, Ohmori Y, Okumura J . Comparison of three nonviral transfection methods for foreign gene expression in early chicken embryos in vivo Biochem Biophys Res Commun 1997 230: 376–380

    Article  CAS  Google Scholar 

  15. Heller R et al. In vivo gene electroinjection and expression in rat liver FEBS Lett 1996 389: 225–228

    Article  CAS  Google Scholar 

  16. Harrison RL . Byrne BJ. Tung L. Electroporation-mediated gene transfer in cardiac tissue FEBS Lett 1998 435: 1–5

    Article  CAS  Google Scholar 

  17. Rols MP et al. In vivo electrically mediated protein and gene transfer in murine melanoma Nat Biotechnol 1998 16: 168–171

    Article  CAS  Google Scholar 

  18. Goto T et al. Highly efficient electro-gene therapy of solid tumor by using an expression plasmid for the herpes simplex virus thymidine kinase gene Proc Natl Acad Sci USA 2000 97: 354–359

    Article  CAS  Google Scholar 

  19. Wells JM et al. Electroporation-enhanced gene delivery in mammary tumors Gene Therapy 2000 7: 541–547

    Article  CAS  Google Scholar 

  20. Rekhter MD et al. Gene transfer into normal and atherosclerotic human blood vessels Circ Res 1998 82: 1243–1252

    Article  CAS  Google Scholar 

  21. von der Leyen HE et al. Gene therapy inhibiting neointimal vascular lesion: in vivo transfer of endothelial cell nitric oxide synthase gene Proc Natl Acad Sci USA 1995 92: 1137–1141

    Article  CAS  Google Scholar 

  22. Matsumoto T et al. Hemagglutinating virus of Japan-liposome-mediated gene transfer of endothelial cell nitric oxide synthase inhibits intimal hyperplasia of canine vein grafts under conditions of poor runoff J Vasc Surg 1998 27: 135–144

    Article  CAS  Google Scholar 

  23. Yonemitsu Y et al. Transfer of wild-type p53 gene effectively inhibits vascular smooth muscle cell proliferation in vitro and in vivo Circ Res 1998 82: 147–156

    Article  CAS  Google Scholar 

  24. Bai H et al. Inhibition of intimal hyperplasia after vein grafting by in vivo transfer of human senescent cell-derived inhibitor-1 gene Gene Therapy 1998 5: 761–769

    Article  CAS  Google Scholar 

  25. Simokawa T, Okamura K, Ra C . DNA induces apoptosis in electroporated human promonocytic cell line U937 Biochem Biophys Res Commun 2000 270: 94–99

    Article  Google Scholar 

  26. Hofmann F et al. Electric field pulses can induce apoptosis J Mem Biol 1999 69: 103–109

    Article  Google Scholar 

  27. Saeki Y, Wataya-Kaneda M, Tanaka K, Kaneda Y . Sustained transgene expression in vitro and in vivo using an Epstein–Barr virus replicon vector system combined with HVJ liposomes Gene Therapy 1998 5: 1031–1037

    Article  CAS  Google Scholar 

  28. Mercer EH et al. The dopamine beta-hydroxylase gene promoter directs expression of E. coli lacZ to sympathetic and other neurons in adult transgenic mice Neuron 1991 7: 703–716

    Article  CAS  Google Scholar 

  29. Saeki Y et al. Development and characterization of cationic liposomes conjugated with HVJ (Sendai virus): reciprocal effect of cationic lipid for in vitro and in vivo gene transfer Hum Gene Ther 1997 8: 2133–2141

    Article  CAS  Google Scholar 

  30. Yonemitsu Y et al. HVJ (Sendai virus)-cationic liposomes: a novel and potentially effective liposome-mediated technique for gene transfer to the airway epithelium Gene Therapy 1997 4: 631–638

    Article  CAS  Google Scholar 

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Acknowledgements

We thank Dr M Ishida, Department of Surgery and Science,Graduate School of Medical Sciences, Kyushu University for technical assistance and M Ohara for useful comments on the manuscript. This work was supported in part by a Grant-in-aid for General Scientific Research from the Ministry of Education, Science, Technology, Sports, and Culture of Japan.

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Authors and Affiliations

  1. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    T Matsumoto, K Komori, T Shoji, S Kuma, M Kume, T Yamaoka, E Mori, T Furuyama & K Sugimachi

  2. Division of Pathophysiological and Experimental Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Y Yonemitsu

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  1. T Matsumoto
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Matsumoto, T., Komori, K., Shoji, T. et al. Successful and optimized in vivo gene transfer to rabbit carotid artery mediated by electronic pulse. Gene Ther 8, 1174–1179 (2001). https://doi.org/10.1038/sj.gt.3301502

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  • DOI: https://doi.org/10.1038/sj.gt.3301502

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