HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Joy Dalesandro Margaret D. Allen Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dalesandro, J. Articles by Allen, M. D. Search for Related Content PubMed PubMed Citation Articles by Dalesandro, J. Articles by Allen, M. D.

J Thorac Cardiovasc Surg 1996;111:416-422
© 1996 Mosby, Inc.

CARDIAC AND PULMONARY REPLACEMENT

GENE THERAPY FOR DONOR HEARTS: EX VIVO LIPOSOME-MEDIATED TRANSFECTION

Seattle, Wash., and Davis, Calif.

Address for reprints: Joy Dalesandro, MD, Division of Cardiothoracic Surgery, University of Washington Medical Center, 1959 N.E. Pacific St., Box 356310, Seattle, WA 98195-6310.

Abstract

Objective: Liposomes may be an appropriate transfection vehicle for transplanted hearts, avoiding the use of viruses in immunosuppressed hosts and allowing transfection of nondividing cells. To study whether liposome-mediated transfection could be accomplished during transplantation, we used a liposome-reporter gene system in a rabbit model of allograft cardiac transplantation. Methods: After aortic crossclamping, Stauffland donor hearts were injected with 10 ml Stanford cardioplegic solution; then a 1.3 to 2.0 mg/kg dose of chloramphenicol acetyl transferase in 1:1 deoxyribonucleic acid–liposome complexes was injected proximal to the aortic crossclamp for coronary artery perfusion. The hearts were transplanted into New Zealand White rabbit recipients in the heterotopic cervical position (n= 11 transplants). Recipients were sacrificed at 24 hours. Myocardial specimens (right and left ventricles) and vascular specimens (epicardial coronary artery, aortic root, and coronary sinus) from both the transplanted and native hearts were analyzed for chloramphenicol acetyl transferase protein by means of the enzymatic liquid scintillation assay (counts per minute per milligram of total protein). Results: In the recipient, myocardial chloramphenicol acetyl transferase activity was significantly greater in treated donor hearts (mean 4.6 x 10⁵cpm/mg ± 1.1 x 10⁵[standard error]) than in native hearts (mean 4.1 x 10²cpm/mg ± 72 [standard error], p< 0.01, Mann-Whitney U test). In treated donor hearts, right and left ventricular specimens, as well as apical and basal myocardial specimens, were transfected equally. Chloramphenicol acetyl transferase activity in vascular specimens also indicated transfection (mean 5.4 x 10⁵cpm/mg ± 2.5 x 10⁵[standard error]). Chloramphenicol acetyl transferase activity in the coronary sinus was comparable with that in the coronary arteries, which suggests that liposomes can traverse the coronary capillary beds. Conclusions: These findings demonstrate that ex vivo transfection of donor hearts with a liposome-reporter gene system results in significant in vivo expression of the transfected gene product after cardiac transplantation. Genetic alteration of myocardium and cardiac vasculature has potential clinical applications in the prevention of posttransplantation rejection, ischemia-reperfusion injury, and both transplant and nontransplant coronary artery disease. (J THORAC CARDIOVASC SURG 1996;111:416-22)

This article has been cited by other articles:

				H. Holschermann, T. H.W. Stadlbauer, A. H. Wagner, H. Fingerhuth, H. Muth, S. Rong, F. Guler, H. Tillmanns, and M. Hecker STAT-1 and AP-1 decoy oligonucleotide therapy delays acute rejection and prolongs cardiac allograft survival Cardiovasc Res, August 1, 2006; 71(3): 527 - 536. [Abstract] [Full Text] [PDF]

				H. Furukawa, K. Oshima, T. Tung, G. Cui, H. Laks, and L. Sen Liposome-Mediated Combinatorial Cytokine Gene Therapy Induces Localized Synergistic Immunosuppression and Promotes Long-Term Survival of Cardiac Allografts J. Immunol., June 1, 2005; 174(11): 6983 - 6992. [Abstract] [Full Text] [PDF]

				V. P. Torchilin, T. S. Levchenko, R. Rammohan, N. Volodina, B. Papahadjopoulos-Sternberg, and G. G. M. D'Souza Cell transfection in vitro and in vivo with nontoxic TAT peptide-liposome-DNA complexes PNAS, February 18, 2003; 100(4): 1972 - 1977. [Abstract] [Full Text] [PDF]

				A. Iwata, S. Sai, Y. Nitta, M. Chen, R. de Fries-Hallstrand, J. Dalesandro, R. Thomas, and M. D. Allen Liposome-Mediated Gene Transfection of Endothelial Nitric Oxide Synthase Reduces Endothelial Activation and Leukocyte Infiltration in Transplanted Hearts Circulation, June 5, 2001; 103(22): 2753 - 2759. [Abstract] [Full Text] [PDF]

				J. Yap, C. Pellegrini, T. O'Brien, H. D. Tazelaar, and C. G.A. McGregor Conditions of vector delivery improve efficiency of adenoviral-mediated gene transfer to the transplanted heart Eur. J. Cardiothorac. Surg., May 1, 2001; 19(5): 702 - 707. [Abstract] [Full Text] [PDF]

				A. S. Shah, D. C. White, O. Tai, J. A. Hata, K. H. Wilson, A. Pippen, A. P. Kypson, D. D. Glower, R. J. Lefkowitz, and W. J. Koch Adenovirus-mediated genetic manipulation of the myocardial {beta}-adrenergic signaling system in transplanted hearts J. Thorac. Cardiovasc. Surg., September 1, 2000; 120(3): 581 - 588. [Abstract] [Full Text] [PDF]

				C. Pellegrini, A. Jeppsson, C. B. Taner, T. O’Brien, V. M. Miller, H. D. Tazelaar, and C. G. A. McGregor HIGHLY EFFICIENT EX VIVO GENE TRANSFER TO THE TRANSPLANTED HEART BY MEANS OF HYPOTHERMIC PERFUSION WITH A LOW DOSE OF ADENOVIRAL VECTOR J. Thorac. Cardiovasc. Surg., March 1, 2000; 119(3): 493 - 500. [Abstract] [Full Text] [PDF]

				M. D. Allen Myocardial protection: is there a role for gene therapy? Ann. Thorac. Surg., November 1, 1999; 68(5): 1924 - 1928. [Abstract] [Full Text] [PDF]

				R. S. Poston, M. Ennen, J. Pollard, E. G. Hoyt, M. E. Billingham, and R. C. Robbins Ex vivo gene therapy prevents chronic graft vascular disease incardiac allografts J. Thorac. Cardiovasc. Surg., September 1, 1998; 116(3): 386 - 390. [Abstract] [Full Text]

				S. Gojo, K. Niwaya, S. Taniguchi, K. Nishizaki, and S. Kitamura Gene Transfer Into the Donor Heart During Cold Preservation for Heart Transplantation Ann. Thorac. Surg., March 1, 1998; 65(3): 647 - 652. [Abstract] [Full Text] [PDF]

				A. P. Kypson, K. Peppel, S. A. Akhter, R. E. Lilly, D. D. Glower, R. J. Lefkowitz, W. J. Koch, and R. W. Anderson Ex Vivo Adenovirus-Mediated Gene Transfer To The Adult Rat Heart J. Thorac. Cardiovasc. Surg., March 1, 1998; 115(3): 623 - 630. [Abstract] [Full Text] [PDF]

				C. H. Boasquevisque, B. N. Mora, M. Bernstein, W. O. Osburn, J. Nietupski, R. K. Scheule, J. D. Cooper, M. Botney, and G. A. Patterson Ex vivo liposome-mediated gene transfer to lung isografts J. Thorac. Cardiovasc. Surg., January 1, 1998; 115(1): 38 - 42. [Abstract] [Full Text] [PDF]

				R. Brauner, M. Nonoyama, H. Laks, D. C. Drinkwater Jr., S. McCaffery, T. Drake, A. J. Berk, L. Sen, and L. Wu INTRACORONARY ADENOVIRUS-MEDIATED TRANSFER OF IMMUNOSUPPRESSIVE CYTOKINE GENES PROLONGS ALLOGRAFT SURVIVAL J. Thorac. Cardiovasc. Surg., December 1, 1997; 114(6): 923 - 933. [Abstract] [Full Text]

				C. H. R. Boasquevisque, T. C. Lee, B. N. Mora, D. Peterson, W. O. Osburn, M. Bernstein, W. Zhang, J. B. Nietupski, R. K. Scheule, J. D. Cooper, et al. LIPOSOME-MEDIATED GENE TRANSFER TO LUNG ISOGRAFTS J. Thorac. Cardiovasc. Surg., November 1, 1997; 114(5): 783 - 792. [Abstract] [Full Text]

				R. Brauner, L. Wu, H. Laks, M. Nonoyama, F. Scholl, O. Shvarts, A. Berk, D. C. Drinkwater Jr., and J.-L. Wang INTRACORONARY GENE TRANSFER OF IMMUNOSUPPRESSIVE CYTOKINES TO CARDIAC ALLOGRAFTS: METHOD AND EFFICACY OF ADENOVIRUS-MEDIATED TRANSDUCTION J. Thorac. Cardiovasc. Surg., June 1, 1997; 113(6): 1059 - 1067. [Abstract] [Full Text]