Skip to main content

Cardiac Gene Delivery in Large Animal Models: Antegrade Techniques

  • Protocol
  • First Online:
Cardiac Gene Therapy

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1521))

Abstract

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

In this chapter, we briefly discuss important elements associated with intracoronary delivery methods and present protocols for three different catheter-based antegrade delivery techniques in a preclinical large animal model. Despite the lower transduction efficacy relative to more invasive delivery techniques, antegrade techniques have the advantage of being clinically well established and having safer profiles which is important when treating patients with cardiac disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

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. doi:10.1089/10430340152528101

    Article  CAS  PubMed  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. doi:10.1038/gt.2012.3

    Article  CAS  PubMed  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  PubMed  PubMed Central  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  PubMed  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  PubMed  PubMed Central  Google Scholar 

  6. 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. doi:10.1007/s12265-013-9479-7

    Article  PubMed  Google Scholar 

  7. Kawase Y, Ly HQ, Prunier F, Lebeche D, Shi Y, Jin 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. doi:10.1016/j.jacc.2007.12.014

    Article  CAS  PubMed  Google Scholar 

  8. 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. doi:10.1126/scitranslmed.3006487

    Article  PubMed  Google Scholar 

  9. Ishikawa K, Fish KM, Tilemann L, Rapti K, Aguero J, Santos-Gallego CG, Lee A, Karakikes I, Xie 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. doi:10.1038/mt.2014.127

    CAS  PubMed  PubMed Central  Google Scholar 

  10. 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. doi:10.1161/CIRCHEARTFAILURE.112.971325

    Article  PubMed  Google Scholar 

  11. 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. doi:10.1016/j.jchf.2013.09.008

    Article  PubMed  Google Scholar 

  12. 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). doi:10.3791/2778

  13. 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. doi:10.1152/ajpheart.00703.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. 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. doi:10.1038/sj.gt.3301079

    Article  CAS  PubMed  Google Scholar 

  15. 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  PubMed  Google Scholar 

  16. 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. doi:10.1038/sj.gt.3301614

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work is supported by NIH P50 HL112324, R01 HL119046, R01 HL117505, R01 HL128099, R01 HL129814, R01HL131404, & T32 HL007824 (R. J. H.), and a Transatlantic Leducq Foundation grant. We would like to acknowledge the Gene Therapy Resource Program (GTRP) of the National Heart, Lung, and Blood Institute, National Institutes of Health for providing some of the gene vectors used in these studies.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kiyotake Ishikawa M.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Science+Business Media New York

About this protocol

Cite this protocol

Watanabe, S., Leonardson, L., Hajjar, R.J., Ishikawa, K. (2017). Cardiac Gene Delivery in Large Animal Models: Antegrade Techniques. In: Ishikawa, K. (eds) Cardiac Gene Therapy. Methods in Molecular Biology, vol 1521. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6588-5_16

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-6588-5_16

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6586-1

  • Online ISBN: 978-1-4939-6588-5

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics