Cardiac Gene Delivery Using DNA–Adenoviral Constructs

  • J. Mark Jones
  • Walter J. Koch
Part of the Methods in Molecular Medicine™ book series (MIMM, volume 112)


In view of the limitations of current cardiac gene transfer techniques by direct myocardial injection, or via the coronary vasculature, we have been attempting to develop potentially clinically applicable methods. Selective catheterization of the coronary arteries has been performed, but the duration of exposure of the heart to the virus is limited. Present systems require high infusion pressure to inject the virus, which could result in endothelial or myocardial injury, and extracardiac transgene expression occurs.

Key Words

Gene transfer intracoronary adenoviral vector coronary catheterization cardiac surgery cardiopulmonary bypass cardiac-selective 


  1. 1.
    Koch, W. J., Lefkowitz, R. J., and Rockman, H. A. (2000) Functional consequences of altering myocardial adrenergic receptor signalling. Annu. Rev. Physiol. 62, 237–260.PubMedCrossRefGoogle Scholar
  2. 2.
    Lefkowitz, R. J., Rockman, H. A., and Koch, W. J. (2000) Catecholamines, cardiac β-adrenergic receptors, and heart failure. Circulation 101, 1634–1637.PubMedGoogle Scholar
  3. 3.
    French, B. A., Mazur, W., Geske, R. S., and Bolli, R. (1994) Direct in vivo gene transfer into porcine myocardium using replication deficient adenoviral vectors. Circulation 90, 2414–2424.PubMedGoogle Scholar
  4. 4.
    Kypson, A. P., Hendrickson, S. C., Akhter, S. A., et al. (1999) Adenoviral-mediated gene transfer of the β2-adrenergic receptor to donor hearts enhances cardiac function. Gene Ther. 6, 1298–1304.PubMedCrossRefGoogle Scholar
  5. 5.
    Maurice, J. P., Hata, J. A., Shah, A. S., et al. (1999) Enhancement of cardiac function after adenoviral-mediated in vivo intracoronary β2-adrenergic receptor gene delivery. J. Clin. Invest. 104, 21–29.PubMedCrossRefGoogle Scholar
  6. 6.
    Shah, A. S., Lilly, E., Kypson, A. P., et al. (2000) Intracoronary adenovirus-mediated delivery and overexpression of the β2-adrenergic receptor in the heart-prospects for molecular ventricular assistance. Circulation 101, 408–414.PubMedGoogle Scholar
  7. 7.
    Barr, E., Carroll, J., Kalynych, A. M., Tripathy, S. K., Kozarsky, K., Wilson, J. M., and Leiden, J. M. (1994) Efficient catheter-mediated gene transfer into the heart using replication-defective adenovirus. Gene Ther. 1, 51–58.PubMedGoogle Scholar
  8. 8.
    Hajjar, R. J., Schmidt, U., Matsui, T., et al. (1998) Modulation of ventricular function through gene transfer in vivo. Proc. Natl. Acad. Sci. USA 95, 5251–5256.PubMedCrossRefGoogle Scholar
  9. 9.
    Lodge, A. J., Chai, P. J., Daggett, C. W., Ungerleider, R. M., and Jaggers, J. (1999) Methylprednisolone reduces the inflammatory response to cardiopulmonary bypass in neonatal piglets: timing of dose is important. J. Thorac. Cardiovasc. Surg. 117, 515–522.PubMedCrossRefGoogle Scholar
  10. 10.
    Donahue, J. K., Kikkawa, K., Johns, D. C., Marban, E., Lawrence, and J. H. (1997) Ultrarapid, highly efficient viral gene transfer to the heart. Proc. Natl. Acad. Sci. USA 94, 4664–4668.PubMedCrossRefGoogle Scholar
  11. 11.
    Jones, J. M., Wilson, K. H., Koch, W. J., and Milano, C. A. (2002) Adenoviral gene transfer to the heart during cardiopulmonary bypass: effect of myocardial protection technique on transgene expression. Eur. J. Cardiothorac. Surg. 21, 847–852.PubMedCrossRefGoogle Scholar
  12. 12.
    Davidson, M. J., Jones, J. M., Emani, S., Wilson, K. H., Jaggers, J., Koch, W. J., and Milano, C. A. (2001) Cardiac gene delivery with cardiopulmonary bypass. Circulation 104, 131–133.PubMedGoogle Scholar
  13. 13.
    Jones, J. M., Wilson, K. M., Steenbergen, C., Koch, W. J., and Milano, C. A. Dose dependent effects of cardiac β2 adrenoceptor gene therapy. J. Surg. Res., in press.Google Scholar
  14. 14.
    Bridges, C. R., Burkman, J. M., Malekan, R., et al. (2002) Global cardiac-specific transgene expression using of cardiopulmonary bypass with cardiac isolation. Ann. Thorac. Surg. 73, 1939–1946.PubMedCrossRefGoogle Scholar
  15. 15.
    Jones, J. M., Petrofski, J. A., Wilson, K. H., Steenbergen, C., Koch, W. J., and Milano, C. A. β2 adrenoreceptor gene therapy ameliorates left ventricular dysfunction following cardiac surgery. Eur. J. Cardiothorac. Surg., in press.Google Scholar
  16. 16.
    Franz, W. M., Rothman, T., Frey, N., and Katus, H. A. (1997) Analysis of tissuespecific gene delivery by recombinant adenoviruses containing cardiac-specific promoters. Cardiovasc. Res. 35, 560–566.PubMedCrossRefGoogle Scholar
  17. 17.
    Phillips, M. I., Tang, Y., Schmidt-Ott, K., Qian, K., and Kagiyama, S. (2002) Vigilant vector: heart-specific promoter in an adeno-associated virus vector for cardioprotection. Hypertension 39, 651–655.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2005

Authors and Affiliations

  • J. Mark Jones
    • 1
  • Walter J. Koch
    • 2
  1. 1.Department of Cardiac Surgery, Royal Victoria Hospital, Belfast, United Kingdomformerly Department of Surgery, Duke University Medical CenterDurhamNC
  2. 2.Center for Translational MedicineThomas Jefferson UniversityPhiladelphiaPA

Personalised recommendations