Skip to main content
Top
Published in: Journal of Cardiovascular Translational Research 8/2014

01-11-2014

A Needleless Liquid Jet Injection Delivery Method for Cardiac Gene Therapy: a Comparative Evaluation Versus Standard Routes of Delivery Reveals Enhanced Therapeutic Retention and Cardiac Specific Gene Expression

Authors: A. S. Fargnoli, M. G. Katz, R. D. Williams, K. B. Margulies, Charles R. Bridges

Published in: Journal of Cardiovascular Translational Research | Issue 8/2014

Login to get access

Abstract

This study evaluates needleless liquid jet method and compares it with three common experimental methods: (1) intramuscular injection (IM), (2) left ventricular intracavitary infusion (LVIC), and (3) LV intracavitary infusion with aortic and pulmonary occlusion (LVIC-OCCL). Two protocols were executed. First (n = 24 rats), retention of dye was evaluated 10 min after delivery in an acute model. The acute study revealed the following: significantly higher dye retention (expressed as % myocardial cross-section area) in the left ventricle in both the liquid jet [52 ± 4] % and LVIC-OCCL [58 ± 3] % groups p < 0.05 compared with IM [31 ± 8] % and LVIC [35 ± 4] %. In the second (n = 16 rats), each animal received adeno-associated virus encoding green fluorescent protein (AAV.EGFP) at a single dose with terminal 6-week endpoint. In the second phase with AAV.EGFP at 6 weeks post-delivery, a similar trend was found with liquid jet [54 ± 5] % and LVIC-OCCL [60 ± 8] % featuring more LV expression as compared with IM [30 ± 9] % and LVIC [23 ± 9] %. The IM and LVIC-OCCL cross sections revealed myocardial fibrosis. With more detailed development in future model studies, needleless liquid jet delivery offers a promising strategy to improve direct myocardial delivery.
Literature
1.
go back to reference Go, A. S., Mozaffarian, D., Roger, V. L., Benjamin, E. J., Berry, J. D., Blaha, M. J., et al. (2014). Heart disease and stroke statistics—2013 update: a report from the American Heart Association. Circulation, 129(3), e28–e292.PubMedCrossRef Go, A. S., Mozaffarian, D., Roger, V. L., Benjamin, E. J., Berry, J. D., Blaha, M. J., et al. (2014). Heart disease and stroke statistics—2013 update: a report from the American Heart Association. Circulation, 129(3), e28–e292.PubMedCrossRef
2.
go back to reference Brinks, H., & Koch, W. J. (2010). βARKct: a therapeutic approach for improved adrenergic signaling and function in heart disease. Journal of Cardiovascular Translational Research, 3, 499–506.PubMedCrossRef Brinks, H., & Koch, W. J. (2010). βARKct: a therapeutic approach for improved adrenergic signaling and function in heart disease. Journal of Cardiovascular Translational Research, 3, 499–506.PubMedCrossRef
3.
go back to reference Kairouz, V., Lipskaia, L., Hajjar, R. J., & Chemaly, E. R. (2012). Molecular targets in heart failure gene therapy: current controversies and translational perspectives. Annals of the New York Academy of Sciences, 1254, 42–50.PubMedCentralPubMedCrossRef Kairouz, V., Lipskaia, L., Hajjar, R. J., & Chemaly, E. R. (2012). Molecular targets in heart failure gene therapy: current controversies and translational perspectives. Annals of the New York Academy of Sciences, 1254, 42–50.PubMedCentralPubMedCrossRef
5.
go back to reference Taimeh, Z., Loughran, J., Birks, E. J., & Bolli, R. (2013). Vascular endothelial growth factor in heart failure. Nature Reviews Cardiology, 10, 519–530.PubMedCrossRef Taimeh, Z., Loughran, J., Birks, E. J., & Bolli, R. (2013). Vascular endothelial growth factor in heart failure. Nature Reviews Cardiology, 10, 519–530.PubMedCrossRef
6.
go back to reference Vatner, S. F. (2005). FGF induces hypertrophy and angiogenesis in hibernating myocardium. Circulation Research, 96, 705–707.PubMedCrossRef Vatner, S. F. (2005). FGF induces hypertrophy and angiogenesis in hibernating myocardium. Circulation Research, 96, 705–707.PubMedCrossRef
7.
go back to reference Jaski, B. E., Jessup, M. L., Mancini, D. M., Cappola, T. P., Pauly, D. F., Greenberg, B., Borow, K., Dittrich, H., Zsebo, K. M., & Hajjar, R. J. (2009). Calcium upregulation by percutaneous administration of gene therapy in cardiac disease (CUPID trial), a first-in-human phase 1/2 clinical trial. Journal of Cardiac Failure, 15, 171–181.PubMedCentralPubMedCrossRef Jaski, B. E., Jessup, M. L., Mancini, D. M., Cappola, T. P., Pauly, D. F., Greenberg, B., Borow, K., Dittrich, H., Zsebo, K. M., & Hajjar, R. J. (2009). Calcium upregulation by percutaneous administration of gene therapy in cardiac disease (CUPID trial), a first-in-human phase 1/2 clinical trial. Journal of Cardiac Failure, 15, 171–181.PubMedCentralPubMedCrossRef
8.
go back to reference Jessup, M., Greenberg, B., Mancini, D., Cappola, T., Pauly, D. F., Jaski, B., et al. (2011). calcium upregulation by percutaneous administration of gene therapy in cardiac disease (CUPID): a phase 2 trial of intracoronary gene therapy of sarcoplasmic reticulum Ca2+-ATPase in patients with advanced heart failure. Circulation, 124, 304–313.PubMedCrossRef Jessup, M., Greenberg, B., Mancini, D., Cappola, T., Pauly, D. F., Jaski, B., et al. (2011). calcium upregulation by percutaneous administration of gene therapy in cardiac disease (CUPID): a phase 2 trial of intracoronary gene therapy of sarcoplasmic reticulum Ca2+-ATPase in patients with advanced heart failure. Circulation, 124, 304–313.PubMedCrossRef
9.
go back to reference Hajjar, R. J., Zsebo, K., Deckelbaum, L., Thompson, C., Rudy, J., Yaroshinsky, A., et al. (2008). Design of a phase 1/2 trial of intracoronary administration of AAV1/SERCA2a in patients with heart failure. Journal of Cardiac Failure, 14(5), 355–367.PubMedCrossRef Hajjar, R. J., Zsebo, K., Deckelbaum, L., Thompson, C., Rudy, J., Yaroshinsky, A., et al. (2008). Design of a phase 1/2 trial of intracoronary administration of AAV1/SERCA2a in patients with heart failure. Journal of Cardiac Failure, 14(5), 355–367.PubMedCrossRef
10.
go back to reference Greelish, J. P., Su, L. T., Lankford, E. B., Burkman, J. M., Chen, H., Konig, S. K., et al. (1999). Stable restoration of the sarcoglycan complex in dystrophic muscle perfused with histamine and a recombinant adeno-associated viral vector. Nature Medicine, 5(4), 439–443.PubMedCrossRef Greelish, J. P., Su, L. T., Lankford, E. B., Burkman, J. M., Chen, H., Konig, S. K., et al. (1999). Stable restoration of the sarcoglycan complex in dystrophic muscle perfused with histamine and a recombinant adeno-associated viral vector. Nature Medicine, 5(4), 439–443.PubMedCrossRef
11.
go back to reference Calcedo, R., Morizono, H., Wang, L., McCarter, R., He, J., Jones, D., et al. (2011). Adeno-associated virus antibody profiles in newborns, children, and adolescents. Clinical and Vaccine Immunology, 18(9), 1586–1588.PubMedCentralPubMedCrossRef Calcedo, R., Morizono, H., Wang, L., McCarter, R., He, J., Jones, D., et al. (2011). Adeno-associated virus antibody profiles in newborns, children, and adolescents. Clinical and Vaccine Immunology, 18(9), 1586–1588.PubMedCentralPubMedCrossRef
12.
go back to reference Boekstegers, P., von Degenfeld, G., Giehrl, W., Kupatt, C., Franz, W., & Steinbeck, G. (2000). Myocardial gene transfer by selective pressure-regulated retroinfusion of coronary veins. Gene Therapy, 7, 232–240.PubMedCrossRef Boekstegers, P., von Degenfeld, G., Giehrl, W., Kupatt, C., Franz, W., & Steinbeck, G. (2000). Myocardial gene transfer by selective pressure-regulated retroinfusion of coronary veins. Gene Therapy, 7, 232–240.PubMedCrossRef
13.
go back to reference Fargnoli, A. S., Katz, M. G., Yarnall, C., Isidro, A., Petrov, M., Steuerwald, N., et al. (2013). Cardiac surgical delivery of the sarcoplasmic reticulum calcium ATPase rescues myocytes in ischemic heart failure. Annals of Thoracic Surgery, 96(2), 586–595.PubMedCentralPubMedCrossRef Fargnoli, A. S., Katz, M. G., Yarnall, C., Isidro, A., Petrov, M., Steuerwald, N., et al. (2013). Cardiac surgical delivery of the sarcoplasmic reticulum calcium ATPase rescues myocytes in ischemic heart failure. Annals of Thoracic Surgery, 96(2), 586–595.PubMedCentralPubMedCrossRef
14.
go back to reference Rosengart, T. K., Lee, L. Y., Patel, S. R., Sanborn, T. A., Parikh, M., Bergman, G. W., et al. (1999). Angiogenesis gene therapy: phase I assessment of direct intramyocardial administration of an adenovirus vector expressing VEGF121 cDNA to individuals with clinically significant severe coronary artery disease. Circulation, 100(5), 468–474.PubMedCrossRef Rosengart, T. K., Lee, L. Y., Patel, S. R., Sanborn, T. A., Parikh, M., Bergman, G. W., et al. (1999). Angiogenesis gene therapy: phase I assessment of direct intramyocardial administration of an adenovirus vector expressing VEGF121 cDNA to individuals with clinically significant severe coronary artery disease. Circulation, 100(5), 468–474.PubMedCrossRef
15.
go back to reference Magovern, C. J., Mack, C. A., Zhang, J., Hahn, R. T., Ko, W., Isom, O. W., et al. (1996). Direct in vivo gene transfer to canine myocardium using a replication-deficient adenovirus vector. Annals of Thoracic Surgery, 62(2), 425–433. discussion 433-4.PubMedCrossRef Magovern, C. J., Mack, C. A., Zhang, J., Hahn, R. T., Ko, W., Isom, O. W., et al. (1996). Direct in vivo gene transfer to canine myocardium using a replication-deficient adenovirus vector. Annals of Thoracic Surgery, 62(2), 425–433. discussion 433-4.PubMedCrossRef
16.
go back to reference Barr, E., Carroll, J., Kalynych, A. M., Tripathy, S. K., Kozarsky, K., Wilson, J. M., et al. (1994). Efficient catheter-mediated gene transfer into the heart using replication-defective adenovirus. Gene Therapy, 1(1), 51–58.PubMed Barr, E., Carroll, J., Kalynych, A. M., Tripathy, S. K., Kozarsky, K., Wilson, J. M., et al. (1994). Efficient catheter-mediated gene transfer into the heart using replication-defective adenovirus. Gene Therapy, 1(1), 51–58.PubMed
17.
go back to reference Matsuno, Y., Iwata, H., Umeda, Y., Takagi, H., Mori, Y., Miyazaki, J., et al. (2003). Nonviral gene gun mediated transfer into the beating heart. ASAIO Journal, 49(6), 641–644.PubMedCrossRef Matsuno, Y., Iwata, H., Umeda, Y., Takagi, H., Mori, Y., Miyazaki, J., et al. (2003). Nonviral gene gun mediated transfer into the beating heart. ASAIO Journal, 49(6), 641–644.PubMedCrossRef
18.
go back to reference Nishizaki, K., Mazda, O., Dohi, Y., Kawata, T., Mizuguchi, K., Kitamura, S., et al. (2000). In vivo gene gun-mediated transduction into rat heart with Epstein-Barr virus-based episomal vectors. Annals of Thoracic Surgery, 70(4), 1332–1337.PubMedCrossRef Nishizaki, K., Mazda, O., Dohi, Y., Kawata, T., Mizuguchi, K., Kitamura, S., et al. (2000). In vivo gene gun-mediated transduction into rat heart with Epstein-Barr virus-based episomal vectors. Annals of Thoracic Surgery, 70(4), 1332–1337.PubMedCrossRef
19.
go back to reference Le Moigne, J., Mount, D. M., Netanyahu, N. S., & Memarsadeghi, N. (2007). A fast implementation of the ISODATA clustering algorithm. International Journal of Computational Geometry and Applications, 17, 71–103.CrossRef Le Moigne, J., Mount, D. M., Netanyahu, N. S., & Memarsadeghi, N. (2007). A fast implementation of the ISODATA clustering algorithm. International Journal of Computational Geometry and Applications, 17, 71–103.CrossRef
20.
go back to reference Grines, C. L., Watkins, M. W., Helmer, G., Penny, W., Brinker, J., Marmur, J. D., et al. (2002). Angiogenic gene therapy (AGENT) trial in patients with stable angina pectoris. Circulation, 105(11), 1291–1297.PubMedCrossRef Grines, C. L., Watkins, M. W., Helmer, G., Penny, W., Brinker, J., Marmur, J. D., et al. (2002). Angiogenic gene therapy (AGENT) trial in patients with stable angina pectoris. Circulation, 105(11), 1291–1297.PubMedCrossRef
21.
go back to reference Vale, P. R., Losordo, D. W., Milliken, C. E., McDonald, M. C., Gravelin, L. M., Curry, C. M., et al. (2001). Randomized, single-blind, placebo-controlled pilot study of catheter-based myocardial gene transfer for therapeutic angiogenesis using left ventricular electromechanical mapping in patients with chronic myocardial ischemia. Circulation, 103(17), 2138–2143.PubMedCrossRef Vale, P. R., Losordo, D. W., Milliken, C. E., McDonald, M. C., Gravelin, L. M., Curry, C. M., et al. (2001). Randomized, single-blind, placebo-controlled pilot study of catheter-based myocardial gene transfer for therapeutic angiogenesis using left ventricular electromechanical mapping in patients with chronic myocardial ischemia. Circulation, 103(17), 2138–2143.PubMedCrossRef
22.
go back to reference Bish, L. T., Sleeper, M. M., Brainard, B., Cole, S., Russell, N., Withnall, E., et al. (2008). Percutaneous transendocardial delivery of self-complementary adeno-associated virus 6 achieves global cardiac gene transfer in canines. Molecular Therapy, 16(12), 1953–1959.PubMedCentralPubMedCrossRef Bish, L. T., Sleeper, M. M., Brainard, B., Cole, S., Russell, N., Withnall, E., et al. (2008). Percutaneous transendocardial delivery of self-complementary adeno-associated virus 6 achieves global cardiac gene transfer in canines. Molecular Therapy, 16(12), 1953–1959.PubMedCentralPubMedCrossRef
23.
go back to reference French, B. A., Mazur, W., Geske, R. S., & Bolli, R. (1994). Direct in vivo gene transfer into porcine myocardium using replication-deficient adenoviral vectors. Circulation, 90(5), 2414–2424.PubMedCrossRef French, B. A., Mazur, W., Geske, R. S., & Bolli, R. (1994). Direct in vivo gene transfer into porcine myocardium using replication-deficient adenoviral vectors. Circulation, 90(5), 2414–2424.PubMedCrossRef
24.
go back to reference Grossman, P. M., Han, Z., Palasis, M., Barry, J. J., & Lederman, R. J. (2002). Incomplete retention after direct myocardial injection. Catheterization and Cardiovascular Interventions, 55(3), 392–397.PubMedCrossRef Grossman, P. M., Han, Z., Palasis, M., Barry, J. J., & Lederman, R. J. (2002). Incomplete retention after direct myocardial injection. Catheterization and Cardiovascular Interventions, 55(3), 392–397.PubMedCrossRef
25.
go back to reference Dixon, J. A., & Spinale, F. G. (2009). Large animal models of heart failure: a critical link in the translation of basic science to clinical practice. Circulation. Heart Failure, 2, 262–271.PubMedCentralPubMedCrossRef Dixon, J. A., & Spinale, F. G. (2009). Large animal models of heart failure: a critical link in the translation of basic science to clinical practice. Circulation. Heart Failure, 2, 262–271.PubMedCentralPubMedCrossRef
26.
go back to reference Guzman, R. J., Lemarchand, P., Crystal, R. G., Epstein, S. E., & Finkel, T. (1993). Efficient gene transfer into myocardium by direct injection of adenovirus vectors. Circulation Research, 73(6), 1202–1207.PubMedCrossRef Guzman, R. J., Lemarchand, P., Crystal, R. G., Epstein, S. E., & Finkel, T. (1993). Efficient gene transfer into myocardium by direct injection of adenovirus vectors. Circulation Research, 73(6), 1202–1207.PubMedCrossRef
27.
go back to reference von Harsdorf, Schott, R. J., Shen, Y. T., Vatner, S. F., Mahdavi, V., & Nadal-Ginard, B. (1993). Gene injection into canine myocardium as a useful model for studying gene expression in the heart of large mammals. Circulation Research, 72(3), 688–695.CrossRef von Harsdorf, Schott, R. J., Shen, Y. T., Vatner, S. F., Mahdavi, V., & Nadal-Ginard, B. (1993). Gene injection into canine myocardium as a useful model for studying gene expression in the heart of large mammals. Circulation Research, 72(3), 688–695.CrossRef
28.
go back to reference Mays, L. E., & Wilson, J. M. (2011). The complex and evolving story of T cell activation to AAV vector-encoded transgene products. Molecular Therapy, 19(1), 16–27.PubMedCentralPubMedCrossRef Mays, L. E., & Wilson, J. M. (2011). The complex and evolving story of T cell activation to AAV vector-encoded transgene products. Molecular Therapy, 19(1), 16–27.PubMedCentralPubMedCrossRef
29.
go back to reference Pfeffer, M. A., & Braunwald, E. (1990). Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications. Circulation, 81, 1161–1172.PubMedCrossRef Pfeffer, M. A., & Braunwald, E. (1990). Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications. Circulation, 81, 1161–1172.PubMedCrossRef
30.
go back to reference Blankinship, M. J., Gregorevic, P., Allen, J. M., Harper, S. Q., Harper, H., Halbert, C. L., et al. (2004). Efficient transduction of skeletal muscle using vectors based on adeno-associated virus serotype 6. Molecular Therapy, 10(4), 671–678.PubMedCrossRef Blankinship, M. J., Gregorevic, P., Allen, J. M., Harper, S. Q., Harper, H., Halbert, C. L., et al. (2004). Efficient transduction of skeletal muscle using vectors based on adeno-associated virus serotype 6. Molecular Therapy, 10(4), 671–678.PubMedCrossRef
31.
go back to reference Wang, Z., Zhu, T., Qiao, C., Zhou, L., Wang, B., Zhang, J., et al. (2005). Adeno-associated virus serotype 8 efficiently delivers genes to muscle and heart. Nature Biotechnology, 23(3), 321–328.PubMedCrossRef Wang, Z., Zhu, T., Qiao, C., Zhou, L., Wang, B., Zhang, J., et al. (2005). Adeno-associated virus serotype 8 efficiently delivers genes to muscle and heart. Nature Biotechnology, 23(3), 321–328.PubMedCrossRef
32.
go back to reference Boekstegers, P., & Kupatt, C. (2004). Current concepts and applications of coronary venous retroinfusions. Basic Research in Cardiology, 99, 373–381.PubMedCrossRef Boekstegers, P., & Kupatt, C. (2004). Current concepts and applications of coronary venous retroinfusions. Basic Research in Cardiology, 99, 373–381.PubMedCrossRef
33.
go back to reference Byrne, M. J., Power, J. M., Preovolos, A., Mariani, J. A., Hajjar, R. J., & Kaye, D. M. (2008). Recirculating cardiac delivery of AAV2/1SERCA2a improves myocardial function in an experimental model of heart failure in large animals. Gene Therapy, 15(23), 1550–1557.PubMedCrossRef Byrne, M. J., Power, J. M., Preovolos, A., Mariani, J. A., Hajjar, R. J., & Kaye, D. M. (2008). Recirculating cardiac delivery of AAV2/1SERCA2a improves myocardial function in an experimental model of heart failure in large animals. Gene Therapy, 15(23), 1550–1557.PubMedCrossRef
34.
go back to reference Liu, Q., Huang, W., Zhang, H., Wang, Y., Zhao, J., Song, A., et al. (2014). Neutralizing antibodies against AAV2, AAV5 and AAV8 in healthy and HIV-1-infected subjects in China: implications for gene therapy using AAV vectors. Gene Therapy. Liu, Q., Huang, W., Zhang, H., Wang, Y., Zhao, J., Song, A., et al. (2014). Neutralizing antibodies against AAV2, AAV5 and AAV8 in healthy and HIV-1-infected subjects in China: implications for gene therapy using AAV vectors. Gene Therapy.
Metadata
Title
A Needleless Liquid Jet Injection Delivery Method for Cardiac Gene Therapy: a Comparative Evaluation Versus Standard Routes of Delivery Reveals Enhanced Therapeutic Retention and Cardiac Specific Gene Expression
Authors
A. S. Fargnoli
M. G. Katz
R. D. Williams
K. B. Margulies
Charles R. Bridges
Publication date
01-11-2014
Publisher
Springer US
Published in
Journal of Cardiovascular Translational Research / Issue 8/2014
Print ISSN: 1937-5387
Electronic ISSN: 1937-5395
DOI
https://doi.org/10.1007/s12265-014-9593-1

Other articles of this Issue 8/2014

Journal of Cardiovascular Translational Research 8/2014 Go to the issue