Skip to main content

Cardiac Gene Delivery in Large Animal Models: Selective Retrograde Venous Injection

  • Protocol
  • First Online:
Cardiac Gene Therapy

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

  • 731 Accesses

Abstract

Delivery of viral vectors to the heart represents a challenging endeavor. Besides vector design, the route of substrate administration is significantly influencing gene delivery success. The selective retrograde venous injection (SRVI) represents one of the most efficient percutaneous delivery strategies for transduction of the anterior left ventricular myocardium. In this chapter, we discuss the advantages and limitations of this vector delivery approach and provide a protocol for selective retrograde venous injection in a preclinical large animal model. As limited transgene expression frequently hampers generation of reliable proof-of-principle data and thus translation, this technique provides a valuable tool to ensure high myocardial transduction in preclinical research.

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 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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

Similar content being viewed by others

References

  1. Pleger ST, Shan C, Ksienzyk J, Bekeredjian R, Boekstegers P, Hinkel R, Schinkel S, Leuchs B, Ludwig J, Qiu G, Weber C, Raake P, Koch WJ, Katus HA, Muller OJ, Most P (2011) Cardiac AAV9-S100A1 gene therapy rescues post-ischemic heart failure in a preclinical large animal model. Sci Transl Med 3(92):92ra64. https://doi.org/10.1126/scitranslmed.3002097

    Article  CAS  Google Scholar 

  2. Raake PW, Schlegel P, Ksienzyk J, Reinkober J, Barthelmes J, Schinkel S, Pleger S, Mier W, Haberkorn U, Koch WJ, Katus HA, Most P, Muller OJ (2013) AAV6.betaARKct cardiac gene therapy ameliorates cardiac function and normalizes the catecholaminergic axis in a clinically relevant large animal heart failure model. Eur Heart J 34(19):1437–1447. https://doi.org/10.1093/eurheartj/ehr447

    Article  CAS  Google Scholar 

  3. Katz MG, Fargnoli AS, Pritchette LA, Bridges CR (2012) Gene delivery technologies for cardiac applications. Gene Ther 19(6):659–669. https://doi.org/10.1038/gt.2012.11

    Article  CAS  Google Scholar 

  4. Fearon WF, Ikeno F, Bailey LR, Hiatt BL, Herity NA, Carter AJ, Fitzgerald PJ, Rezaee M, Yeung AC, Yock PG (2004) Evaluation of high-pressure retrograde coronary venous delivery of FGF-2 protein. Catheter Cardiovasc Interv 61(3):422–428. https://doi.org/10.1002/ccd.10790

    Article  Google Scholar 

  5. 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 

  6. Sasano T, Kikuchi K, McDonald AD, Lai S, Donahue JK (2007) Targeted high-efficiency, homogeneous myocardial gene transfer. J Mol Cell Cardiol 42(5):954–961. https://doi.org/10.1016/j.yjmcc.2007.02.004

    Article  CAS  Google Scholar 

  7. 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 

  8. Raake P, von Degenfeld G, Hinkel R, Vachenauer R, Sandner T, Beller S, Andrees M, Kupatt C, Schuler G, Boekstegers P (2004) Myocardial gene transfer by selective pressure-regulated retroinfusion of coronary veins: comparison with surgical and percutaneous intramyocardial gene delivery. J Am Coll Cardiol 44(5):1124–1129. https://doi.org/10.1016/j.jacc.2004.05.074

    Article  CAS  Google Scholar 

  9. 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 Therap 20(3):565–571. https://doi.org/10.1038/mt.2011.268

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work is supported by grants from the Deutsche Forschungsgemeinschaft (RA 1668/1-1 and RA 1668/3-1) to P.W.R.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Philip W. J. Raake .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Schlegel, P., Raake, P.W.J. (2022). Cardiac Gene Delivery in Large Animal Models: Selective Retrograde Venous Injection. 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_13

Download citation

  • DOI: https://doi.org/10.1007/978-1-0716-2707-5_13

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-2706-8

  • Online ISBN: 978-1-0716-2707-5

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics