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Standard heparin, low molecular weight heparin, low molecular weight heparinoid, and recombinant hirudin differ in their ability to inhibit transduction by recombinant adeno-associated virus type 2 vectors

Gene Therapy volume 8, pages 966–968 (2001)Cite this article

Abstract

Recombinant adeno-associated virus type 2 (rAAV) is a promising vector for in vivo gene therapy. Transduction by rAAV requires binding to heparan sulfate proteoglycan on the cell surface, and heparin can block this binding. Because heparin is administered to most patients undergoing cardiovascular gene transfer in order to prevent thrombotic events, it is important to identify anticoagulants which do not interfere with rAAV transduction. Therefore, we examined the influence of different anticoagulants on rAAV transduction in vitro. rAAV transduction was inhibited by 40.5 ± 7.9% at heparin concentrations of 0.1 U/ml, and by 81.7 ± 3.6% at 1.0 U/ml. The low molecular weight (LMW) heparin tinzaparin inhibited rAAV transduction by 20.2 ± 3.8% at 0.1 U/ml and 37.1 ± 1.8% at 1.0 U/ml. The inhibitory effect was significantly weaker compared with heparin at 1.0 U/ml, (P < 0.01). The LMW heparinoid danaparoid inhibited rAAV transduction by 8.8 ± 3.5% at 0.1 U/ml (P < 0.01 compared with heparin). In contrast, recombinant hirudin did not interfere at all with rAAV transduction. In summary, the results demonstrate that inhibition of rAAV transduction by heparin occurs rapidly and at therapeutically used concentrations. LMW heparinoids and above all recombinant hirudin might be alternatives for heparin when vascular gene transfer with rAAV requires transient anticoagulation.

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Acknowledgements

This work was supported by the Deutsche Forschungsgemeinschaft grant number RE 1424/1–1 to HR and MH, by the Deutsche Forschungsgemeinschaft grant number SFB 455 and Bayerische Forschungsstiftung grant number VV5 to MH and by Thiemann Arzneimittel, Germany. We thank Dr RJ Samulski for providing the plasmid pXX6, Dr S King for most helpful discussions, and Karin Messerer for excellent technical assistance.

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  1. UT Hacker and FM Gerner: UTH and FMG contributed equally to this work

Authors and Affiliations

  1. Gene Center of the Ludwig-Maximilians-University Munich, Munich, Germany

    UT Hacker, FM Gerner, H Büning, M Hutter & M Hallek

  2. Medical Department III, University Hospital Munich/Grosshadern, Ludwig-Maximilians-University, Munich, Germany

    UT Hacker & M Hallek

  3. Department of Cardiac Surgery, University Hospital Munich/Grosshadern, Ludwig-Maximilians-University, Munich, Germany

    FM Gerner & H Reichenspurner

  4. Department of Surgery, University Hospital Munich/Grosshadern, Ludwig-Maximilians-University, Munich, Germany

    M Stangl

  5. GSF, National Research Center for Environment and Health, Munich, Germany

    M Hallek

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  1. UT Hacker
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Hacker, U., Gerner, F., Büning, H. et al. Standard heparin, low molecular weight heparin, low molecular weight heparinoid, and recombinant hirudin differ in their ability to inhibit transduction by recombinant adeno-associated virus type 2 vectors. Gene Ther 8, 966–968 (2001). https://doi.org/10.1038/sj.gt.3301466

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