Cardiac Gene Delivery in Large Animal Models: Antegrade Techniques

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Cardiac Gene Therapy

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2573))

Abstract

Percutaneous antegrade coronary injection is among the least invasive cardiac selective gene delivery methods. However, the transduction efficiency of a simple bolus antegrade injection is quite low. In order to improve transduction efficiency in antegrade intracoronary delivery, several additional approaches have been proposed.

In this chapter, we will describe the important elements associated with intracoronary delivery methods and present protocols for three different catheter-based antegrade gene delivery techniques in a preclinical large animal model. This is the second edition of this chapter, and it includes modifications we have made over the past several years that further enhance transduction efficacy.

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References

  1. Logeart D, Hatem SN, Heimburger M, Le Roux A, Michel JB, Mercadier JJ (2001) How to optimize in vivo gene transfer to cardiac myocytes: mechanical or pharmacological procedures? Hum Gene Ther 12(13):1601–1610. https://doi.org/10.1089/10430340152528101

    Article  CAS  Google Scholar 

  2. Ishikawa K, Tilemann L, Ladage D, Aguero J, Leonardson L, Fish K, Kawase Y (2012) Cardiac gene therapy in large animals: bridge from bench to bedside. Gene Ther 19(6):670–677. https://doi.org/10.1038/gt.2012.3

    Article  CAS  Google Scholar 

  3. Donahue JK, Kikkawa K, Johns DC, Marban E, Lawrence JH (1997) Ultrarapid, highly efficient viral gene transfer to the heart. Proc Natl Acad Sci U S A 94(9):4664–4668

    Article  CAS  Google Scholar 

  4. Emani SM, Shah AS, Bowman MK, Emani S, Wilson K, Glower DD, Koch WJ (2003) Catheter-based intracoronary myocardial adenoviral gene delivery: importance of intraluminal seal and infusion flow rate. Mol Ther 8(2):306–313

    Article  CAS  Google Scholar 

  5. Hajjar RJ, Schmidt U, Matsui T, Guerrero JL, Lee KH, Gwathmey JK, Dec GW, Semigran MJ, Rosenzweig A (1998) Modulation of ventricular function through gene transfer in vivo. Proc Natl Acad Sci U S A 95(9):5251–5256

    Article  CAS  Google Scholar 

  6. Tilemann L, Lee A, Ishikawa K, Aguero J, Rapti K, Santos-Gallego C, Kohlbrenner E, Fish KM, Kho C, Hajjar RJ (2013) SUMO-1 gene transfer improves cardiac function in a large-animal model of heart failure. Sci Transl Med 5(211):211ra159. https://doi.org/10.1126/scitranslmed.3006487

    Article  CAS  Google Scholar 

  7. Kawase Y, Ly HQ, Prunier F, Lebeche D, Shi Y, ** H, Hadri L, Yoneyama R, Hoshino K, Takewa Y, Sakata S, Peluso R, Zsebo K, Gwathmey JK, Tardif JC, Tanguay JF, Hajjar RJ (2008) Reversal of cardiac dysfunction after long-term expression of SERCA2a by gene transfer in a pre-clinical model of heart failure. J Am Coll Cardiol 51(11):1112–1119. https://doi.org/10.1016/j.jacc.2007.12.014

    Article  CAS  Google Scholar 

  8. Ishikawa K, Fish KM, Tilemann L, Rapti K, Aguero J, Santos-Gallego CG, Lee A, Karakikes I, **e C, Akar FG, Shimada YJ, Gwathmey JK, Asokan A, McPhee S, Samulski J, Samulski RJ, Sigg DC, Weber T, Kranias EG, Hajjar RJ (2014) Cardiac I-1c overexpression with reengineered AAV improves cardiac function in swine ischemic heart failure. Mol Ther 22(12):2038–2045. https://doi.org/10.1038/mt.2014.127

    Article  CAS  Google Scholar 

  9. Fish KM, Ladage D, Kawase Y, Karakikes I, Jeong D, Ly H, Ishikawa K, Hadri L, Tilemann L, Muller-Ehmsen J, Samulski RJ, Kranias EG, Hajjar RJ (2013) AAV9.I-1c delivered via direct coronary infusion in a porcine model of heart failure improves contractility and mitigates adverse remodeling. Circ Heart Fail 6(2):310–317. https://doi.org/10.1161/CIRCHEARTFAILURE.112.971325

    Article  Google Scholar 

  10. Greenberg B, Yaroshinsky A, Zsebo KM, Butler J, Felker GM, Voors AA, Rudy JJ, Wagner K, Hajjar RJ (2014) Design of a phase 2b trial of intracoronary administration of AAV1/SERCA2a in patients with advanced heart failure: the CUPID 2 trial (calcium up-regulation by percutaneous administration of gene therapy in cardiac disease phase 2b). JACC Heart Fail 2(1):84–92. https://doi.org/10.1016/j.jchf.2013.09.008

    Article  Google Scholar 

  11. Ishikawa K, Aguero J, Naim C, Fish K, Hajjar RJ (2013) Percutaneous approaches for efficient cardiac gene delivery. J Cardiovasc Transl Res 6(4):649–659. https://doi.org/10.1007/s12265-013-9479-7

    Article  Google Scholar 

  12. Hammond HK, Penny WF, Traverse JH, Henry TD, Watkins MW, Yancy CW, Sweis RN, Adler ED, Patel AN, Murray DR, Ross RS, Bhargava V, Maisel A, Barnard DD, Lai NC, Dalton ND, Lee ML, Narayan SM, Blanchard DG, Gao MH (2016) Intracoronary gene transfer of adenylyl cyclase 6 in patients with heart failure: a randomized clinical trial. JAMA Cardiol 1(2):163–171. https://doi.org/10.1001/jamacardio.2016.0008

    Article  Google Scholar 

  13. Hulot JS, Salem JE, Redheuil A, Collet JP, Varnous S, Jourdain P, Logeart D, Gandjbakhch E, Bernard C, Hatem SN, Isnard R, Cluzel P, Le Feuvre C, Leprince P, Hammoudi N, Lemoine FM, Klatzmann D, Vicaut E, Komajda M, Montalescot G, Lompre AM, Hajjar RJ, Investigators A-H (2017) Effect of intracoronary administration of AAV1/SERCA2a on ventricular remodelling in patients with advanced systolic heart failure: results from the AGENT-HF randomized phase 2 trial. Eur J Heart Fail 19(11):1534–1541. https://doi.org/10.1002/ejhf.826

    Article  CAS  Google Scholar 

  14. Lyon AR, Babalis D, Morley-Smith AC, Hedger M, Suarez Barrientos A, Foldes G, Couch LS, Chowdhury RA, Tzortzis KN, Peters NS, Rog-Zielinska EA, Yang HY, Welch S, Bowles CT, Rahman Haley S, Bell AR, Rice A, Sasikaran T, Johnson NA, Falaschetti E, Parameshwar J, Lewis C, Tsui S, Simon A, Pepper J, Rudy JJ, Zsebo KM, Macleod KT, Terracciano CM, Hajjar RJ, Banner N, Harding SE (2020) Investigation of the safety and feasibility of AAV1/SERCA2a gene transfer in patients with chronic heart failure supported with a left ventricular assist device – the SERCA-LVAD TRIAL. Gene Ther 27(12):579–590. https://doi.org/10.1038/s41434-020-0171-7

    Article  CAS  Google Scholar 

  15. Ishikawa K, Ladage D, Tilemann L, Fish K, Kawase Y, Hajjar RJ (2011) Gene transfer for ischemic heart failure in a preclinical model. J Vis Exp 51. https://doi.org/10.3791/2778

  16. Hayase M, Del Monte F, Kawase Y, Macneill BD, McGregor J, Yoneyama R, Hoshino K, Tsuji T, De Grand AM, Gwathmey JK, Frangioni JV, Hajjar RJ (2005) Catheter-based antegrade intracoronary viral gene delivery with coronary venous blockade. Am J Physiol Heart Circ Physiol 288(6):H2995–H3000. https://doi.org/10.1152/ajpheart.00703.2004

    Article  CAS  Google Scholar 

  17. Boekstegers P, von Degenfeld G, Giehrl W, Heinrich D, Hullin R, Kupatt C, Steinbeck G, Baretton G, Middeler G, Katus H, Franz WM (2000) Myocardial gene transfer by selective pressure-regulated retroinfusion of coronary veins. Gene Ther 7(3):232–240. https://doi.org/10.1038/sj.gt.3301079

    Article  CAS  Google Scholar 

  18. Shah AS, White DC, Emani S, Kypson AP, Lilly RE, Wilson K, Glower DD, Lefkowitz RJ, Koch WJ (2001) In vivo ventricular gene delivery of a beta-adrenergic receptor kinase inhibitor to the failing heart reverses cardiac dysfunction. Circulation 103(9):1311–1316

    Article  CAS  Google Scholar 

  19. Bennicelli J, Wright JF, Komaromy A, Jacobs JB, Hauck B, Zelenaia O, Mingozzi F, Hui D, Chung D, Rex TS, Wei Z, Qu G, Zhou S, Zeiss C, Arruda VR, Acland GM, Dell’Osso LF, High KA, Maguire AM, Bennett J (2008) Reversal of blindness in animal models of leber congenital amaurosis using optimized AAV2-mediated gene transfer. Mol Ther 16(3):458–465. https://doi.org/10.1038/sj.mt.6300389

    Article  CAS  Google Scholar 

  20. Karakikes I, Hadri L, Rapti K, Ladage D, Ishikawa K, Tilemann L, Yi GH, Morel C, Gwathmey JK, Zsebo K, Weber T, Kawase Y, Hajjar RJ (2012) Concomitant intravenous nitroglycerin with intracoronary delivery of AAV1.SERCA2a enhances gene transfer in porcine hearts. Mol Ther 20(3):565–571. https://doi.org/10.1038/mt.2011.268

    Article  CAS  Google Scholar 

  21. Wright MJ, Wightman LM, Latchman DS, Marber MS (2001) In vivo myocardial gene transfer: optimization and evaluation of intracoronary gene delivery in vivo. Gene Ther 8(24):1833–1839. https://doi.org/10.1038/sj.gt.3301614

    Article  CAS  Google Scholar 

  22. Watanabe S, Leonardson L, Hajjar RJ, Ishikawa K (2017) Cardiac Gene Delivery in Large Animal Models: Antegrade Techniques. Methods Mol Biol 1521:227–235. https://doi.org/10.1007/978-1-4939-6588-5_16

    Article  CAS  Google Scholar 

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Acknowledgments

This work was supported by NIH R01 HL139963 (K.I). We acknowledge the Gene Therapy Resource Program (GTRP) of the National Heart, Lung, and Blood Institute, National Institutes of Health for providing the gene vectors used in this study. S.A.M. was supported by National Institutes of Health T32 HL007824-23.

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Correspondence to Kiyotake Ishikawa .

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Mavropoulos, S.A., Yamada, K.P., Sakata, T., Ishikawa, K. (2022). Cardiac Gene Delivery in Large Animal Models: Antegrade Techniques. In: Ishikawa, K. (eds) Cardiac Gene Therapy. Methods in Molecular Biology, vol 2573. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2707-5_11

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  • DOI: https://doi.org/10.1007/978-1-0716-2707-5_11

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-2706-8

  • Online ISBN: 978-1-0716-2707-5

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