Sonoporation: Mechanical DNA Delivery by Ultrasonic Cavitation

Abstract

Development of nonviral gene transfer methods would be a valuable addition to the gene-therapy armamentarium, particularly for localized targeting of specific tissue volumes. Ultrasound can produce a variety of nonthermal bioeffects via acoustic cavitation including DNA delivery. Cavitation bubbles may induce cell death or transient membrane permeabilization (sonoporation) on a single cell level, as well as microvascular hemorrhage and disruption of tissue structure. Application of sonoporation for gene delivery to cells requires control of cavitation activity. Many studies have been performed using in vitro exposure systems, for which cavitation is virtually ubiquitous. In vivo, cavitation initiation and control is more difficult, but can be enhanced by cavitation nucleation agents, such as an ultrasound contrast agent. Sonoporation and ultrasonically enhanced gene delivery has been reported for a wide range of conditions including low frequency sonication (kilohertz frequencies), lithotripter shockwaves, HIFU, and evendiagnostic ultrasound (megahertz frequencies). In vitro, a variety of cell lines has been successfully transfected, with concomitant cell killing. In vivo, initial applications have been to cancer gene therapy, for which cell killing can be a useful simultaneous treatment, and to cardiovascular disease. The use of ultrasound for nonviral gene delivery has been demonstrated for a robust array of in vitro and mammalian systems, which provides a fundamental basis and strong promise for development of new gene therapy methods for clinical medicine.

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Literature Cited

  1. 1.

    Nabel EG. Circulation 1995; 91:541–548.

    Google Scholar 

  2. 2.

    Schneider MD, French B. Circulation 1993; 88:1937–1942.

    Google Scholar 

  3. 3.

    Gershon H, Ghirlando R, Gutman SB et al. Biochemistry 1993; 32:7143–7151.

    Google Scholar 

  4. 4.

    Chang DC, Reese TS. Biophys J 1990; 58:1–12.

    Google Scholar 

  5. 5.

    Daniell H. Methods Enzymol 1993; 217:536–557.

    Google Scholar 

  6. 6.

    Newman CM, Lawrie A, Brisken AF et al. Echocardiography 2001; 18:339–347.

    Google Scholar 

  7. 7.

    Kim HJ, Greenleaf JF, Kinnick RR et al. Hum Gene Ther 1996; 7:1339–1346.

    Google Scholar 

  8. 8.

    Bao S, Thrall BD, Miller DL. Ultrasound Med Biol 1997; 23:953–959.

    Google Scholar 

  9. 9.

    Tata DB, Dunn F, Tindall DJ. Biochem Biophys Res Comm 1997; 234:64–67.

    Google Scholar 

  10. 10.

    Greenleaf, WJ, Bolander ME, Sarkar G et al. Ultrasound Med Biol 1998; 24:587–595.

    Google Scholar 

  11. 11.

    Mukherjee D, Wong J, Griffin B et al. J Am Coll Cardiol 2000; 35:1678–1686.

    Google Scholar 

  12. 12.

    Porter TR, Iversen PL, Li S et al. J Ultrasound Med 1996; 15:577–584.

    Google Scholar 

  13. 13.

    Lawrie A, Briskin AF, Francis SE et al. Gene Ther 2000; 7:2023–2027.

    Google Scholar 

  14. 14.

    Shohet RV, Chen S, Zhou Y et al. Circulation 2000; 101:2554–2556.

    Google Scholar 

  15. 15.

    Yamasaki K, Tachibana T, Taniyama Y. Circulation 2000; 102:II-247.

    Google Scholar 

  16. 16.

    Komamura K, Tatsumi R, Miyatake K. Circulation 2000; 102:II-561.

    Google Scholar 

  17. 17.

    Taniyama Y, Tachibana K, Yamamoto K. Circulation 2000; 102:II-164.

    Google Scholar 

  18. 18.

    Amabile PG, Waugh JM, Lewis TN et al. Circulation 2000; 102:II-147.

    Google Scholar 

  19. 19.

    Fu YK, Kaufman GE, Miller MW et al. Radiat Res 1979; 80:575–580.

    Google Scholar 

  20. 20.

    Mortimer AJ, Dyson M. Ultrasound Med Biol 1988; 14:499–506.

    Google Scholar 

  21. 21.

    Dinno MA, Crum LA, Wu J. Ultrasound Med Biol 1989; 15:461–470.

    Google Scholar 

  22. 22.

    Mihran RT, Barnes FS, Wachtel H. Ultrasound Med Biol 1990; 16:297–309.

    Google Scholar 

  23. 23.

    Pohl EE, Rosenfeld EH, Pohl P et al. Ultrasound Med Biol 1995; 21:711–719.

    Google Scholar 

  24. 24.

    Kaufman GE, Miller MW. Ultrasound Med Biol 1978 4:139–144.

    Google Scholar 

  25. 25.

    Miller DL, Thomas RM, Buschbom RL. Ultrasound Med Biol 1995; 21:841–848.

    Google Scholar 

  26. 26.

    Liebeskind D, Bases R, Mendez F et al. Science 1979; 205:1273–1275.

    Google Scholar 

  27. 27.

    Miller MW, Miller DL, Brayman AA. Ultrasound Med Biol 1996; 22:1131–1154.

    Google Scholar 

  28. 28.

    Kaufman GE. Ultrasound Med Biol 1985; 11:497–501.

    Google Scholar 

  29. 29.

    Dalecki D, Keller BB, Raeman CH et al. Ultrasound Med Biol 1993; 19:385–390.

    Google Scholar 

  30. 30.

    MacRobbie AG, Raeman CH, Child SZ et al. Ultrasound Med Biol 1997; 23:761–765.

    Google Scholar 

  31. 31.

    Skyba DM, Price RJ, Linka AZ et al. Circulation 1998; 98:290–293.

    Google Scholar 

  32. 32.

    Miller DL, Quddus J. Proc Natl Acad Sci USA 2000; 97:10179–10184.

    Google Scholar 

  33. 33.

    Hynynen K, Chung AH, Colucci V et al. Ultrasound Med Biol 1996; 22:193–201.

    Google Scholar 

  34. 34.

    Child SZ, Hartman CL, Schery LA et al. Ultrasound Med Biol 1990; 16:817–825.

    Google Scholar 

  35. 35.

    Tarantal AF, Canfield DR. Ultrasound Med Biol 1994; 20:65–72.

    Google Scholar 

  36. 36.

    Zachary JF, O'Brien WD, Jr. Vet Pathol 1995; 32:43–54.

    Google Scholar 

  37. 37.

    Miller DL, Thomas RM. Ultrasound Med Biol 1995; 21:249–257.

    Google Scholar 

  38. 38.

    Dalecki D, Child SZ, Raeman CH et al. J Acoust Soc Am 1995; 97:3165–3170.

    Google Scholar 

  39. 39.

    Ramnarine KV, Nassiri DK, McCarthy A et al. Ultrasound Med Biol 1998; 24:575–585.

    Google Scholar 

  40. 40.

    Tsirulnikov EM, Vartanyan IA, Gersuni GV et al. Ultrasound Med Biol 1998; 14:277–285.

    Google Scholar 

  41. 41.

    Nilsson AM, Odselius R, Roijer A et al. Ultrasound Med Biol 1995; 21:833–840.

    Google Scholar 

  42. 42.

    Tachibana K, Tachibana S. Circulation 1995; 92:1148.

    Google Scholar 

  43. 43.

    Harrison GH, Balcer-Kubiczek EK, Eddy HA. Int J Rad Biol 1991; 59:1453–1466.

    Google Scholar 

  44. 44.

    Saad AH, Hahn GM. Ultrasound Med Biol 1992; 18:715–723.

    Google Scholar 

  45. 45.

    Price RJ, Skyba DM, Kaul S et al. Circulation 1998; 98:1264–1267.

    Google Scholar 

  46. 46.

    Unger EC, McCreery TP, Sweitzer RH et al. Invest Radiol 1998; 33:886–892.

    Google Scholar 

  47. 47.

    Ter Haar G. Ultrasound Med Biol 1995; 21:1089–1100.

    Google Scholar 

  48. 48.

    Bender LF, Janes JM, Herrick JF. Arch Phys Med Rehabil 1954; 35:555.

    Google Scholar 

  49. 49.

    Duarte LR. Arch Orthop Trauma Surg 1983; 101:153–159.

    Google Scholar 

  50. 50.

    Nyborg WL, Carson PL, Miller MW et al. Biological Effects of Ultrasound: Mechanisms and Clinical Implications, Report No. 74, National Council on Radiation Protection and Measurements, Bethesda, MD, 1983.

    Google Scholar 

  51. 51.

    Nyborg WL, Carson PL, Miller MW et al. Exposure Criteria for Medical Diagnostic Ultrasound: I. Criteria Based on Thermal Mechanisms, National Council on Radiation Protection Report No 113, Bethesda, MD, 1992.

  52. 52.

    American Institute of Ultrasound in Medicine. J Ultrasound Med 2000; 19:69–168.

    Google Scholar 

  53. 53.

    Ter Haar G, Duck FA. (eds.). The Safe Use of Ultrasound in Medical Diagnosis, British Medical Ultrasound Society/The British Institute of Radiology, London, 2000.

  54. 54.

    Whittingham TA. in Ultrasound in Medicine, FA Duck, AC Baker, HC Staritt (eds.), Institute of Physics Publishing, Philadelphia, 1998.

    Google Scholar 

  55. 55.

    Dalecki D, Child SZ, Raeman CH et al. Ultrasound Med Biol 1997; 23:777–781.

    Google Scholar 

  56. 56.

    Roy RA, Atchley AA, Crum LA et al. J Acoust Soc Am 1985; 78:1799–1805.

    Google Scholar 

  57. 57.

    Clarke PR, Hill CR. J Acoust Soc Am 1970; 47:649–653.

    Google Scholar 

  58. 58.

    Fechheimer M, Denny D, Murphy RF et al. Eur J Cell Biol 1986; 40:242–247.

    Google Scholar 

  59. 59.

    Fechheimer M, Boylan JF, Parker S et al. Proc Natl Acad Sci USA 1987; 84:8463–8467.

    Google Scholar 

  60. 60.

    Johannes C, Obe G. Mutat Res 1997; 374:245–251.

    Google Scholar 

  61. 61.

    Delius M. Shock Waves 1994; 4:55–72.

    Google Scholar 

  62. 62.

    Gambihler S, Delius M, Ellwart JW. J Memb Biol 1994; 141:267–275.

    Google Scholar 

  63. 63.

    Delius M, Adams G. Cancer Res 1999; 59:5227–5232.

    Google Scholar 

  64. 64.

    Miller DL, Williams AR, Morris JE et al. Ultrasonics 1998; 36:947–952.

    Google Scholar 

  65. 65.

    Zhong P, Haifan L, Xi X et al. J Acoust Soc Am 1999; 105:1997–2009.

    Google Scholar 

  66. 66.

    Doukas AG, Flotte TJ. Ultrasound Med Biol 1996; 22:151–164.

    Google Scholar 

  67. 67.

    Lee S, McAuliffe DJ, Zhang H et al. Ultrasound Med Biol 1997; 23:1089–1094.

    Google Scholar 

  68. 68.

    Mulholland SE, Lee S, McAuliffe DJ et al. Pharm Res 1999; 16:514–518.

    Google Scholar 

  69. 69.

    Miller DL, Bao S, Morris JE. Ultrasound Med Biol 1999; 25:143–149.

    Google Scholar 

  70. 70.

    Ward M, Wu J, Chiu J. J Acoust Soc Am 1999; 105:2951–2957.

    Google Scholar 

  71. 71.

    Ward M, Wu J, Chiu J. Ultrasound Med Biol 2000; 26:1169–1175.

    Google Scholar 

  72. 72.

    Miller DL, Quddus J. Ultrasound Med Biol 2000; 26:661–667.

    Google Scholar 

  73. 73.

    Joersbo M, Brunstedt J. Plant Cell Rep 1990; 9:207–210.

    Google Scholar 

  74. 74.

    Joersbo M, Brunstedt J. Physiol Plantar 1992; 85:230–234.

    Google Scholar 

  75. 75.

    Joersbo M, Brunstedt J. J Virol Methods 1990; 29:63–69.

    Google Scholar 

  76. 76.

    Zhang L, Cheng L, Xu N, Zhao N et al. Biotechnology 1991; 9:996–997.

    Google Scholar 

  77. 77.

    Wyber JA, Andrews J, D'Emanuele A. Pharma Res 1997; 14:750–756.

    Google Scholar 

  78. 78.

    Lauer U, Burgelt E, Squire Z et al. Gene Ther 1997; 4:710–715.

    Google Scholar 

  79. 79.

    Miller DL, Bao S, Gies RA et al. Ultrasound Med Biol 1999; 25:1425–1430.

    Google Scholar 

  80. 80.

    Huber PE, Jenne J, Debus J et al. Ultrasound Med Biol 1999; 25:1451–1457.

    Google Scholar 

  81. 81.

    Huber PE, Pfisterer P. Gene Ther 2000; 7:1516–1525.

    Google Scholar 

  82. 82.

    Lawrie A, Briskin AF, Francis SE et al. Circulation 1999; 99:2617–2620.

    Google Scholar 

  83. 83.

    Manome Y, Nakamura M, Ohno T et al. Hum Gene Ther 2000; 11:1521–1528.

    Google Scholar 

  84. 84.

    Koch S, Pohl P, Cobet U et al. Ultrasound Med Biol 2000; 26:897–903.

    Google Scholar 

  85. 85.

    Delius M, Hofschneider P, Lauer U et al. Lancet 1995; 345:1377.

    Google Scholar 

  86. 86.

    Bao S, Thrall BD, Gies RA et al. Cancer Res 1998; 58:219–221.

    Google Scholar 

  87. 87.

    Anwer K, Kao G, Proctor B, Anscombe I et al. Gene Ther 2000; 7:1833–1839.

    Google Scholar 

  88. 88.

    Tomizawa M, Ebara M, Saisho H et al. Cancer Lett 2001; 173:31–38.

    Google Scholar 

  89. 89.

    Porter TR, Kricsfeld D, Xie F. J Am Soc Echocardiogr 2000; 13:434.

    Google Scholar 

  90. 90.

    Cooper MJ. Semin Oncol 1996; 23:172–187.

    Google Scholar 

  91. 91.

    Berinstein NL. Biological therapy of cancer, In The Basic Science of Oncology, 3rd edn., IF Tannock, RP Hill (eds.), McGraw Hill, New York, Chap. 18, 1998.

    Google Scholar 

  92. 92.

    Nomura T, Nakajima S, Kawabata K et al. Cancer Res 1997; 57:2681–2686.

    Google Scholar 

  93. 93.

    Yang JP, Huang L. Gene Ther 1996; 3:542–548.

    Google Scholar 

  94. 94.

    Rakhmilevich AL, Turner J, Ford MJ et al. Proc Natl Acad Sci USA 1996; 93:6291–6296.

    Google Scholar 

  95. 95.

    Nishi T, Yoshizato K, Yamashrio S et al. Cancer Res 1996; 56:1050–1055.

    Google Scholar 

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Miller, D.L., Pislaru, S.V. & Greenleaf, J.F. Sonoporation: Mechanical DNA Delivery by Ultrasonic Cavitation. Somat Cell Mol Genet 27, 115–134 (2002). https://doi.org/10.1023/A:1022983907223

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Keywords

  • Gene Delivery
  • Ultrasound Contrast Agent
  • Cancer Gene Therapy
  • Ultrasonic Cavitation
  • Gene Transfer Method