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Heart-targeted adeno-associated viral vectors selected by in vivo biopanning of a random viral display peptide library

Gene Therapy volume 17, pages 980–990 (2010)Cite this article

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Abstract

Selection of targeted vectors from virus display peptide libraries is a versatile and efficient approach to improve vector specificity and efficiency. This strategy has been used to target various cell types in vitro. Here, we report the screening of an adeno-associated virus type 2 (AAV2) display peptide library in vivo to select vectors specifically homing to heart tissue after systemic application in mice. Selected library clones indicated superior specificity of gene transfer compared with wild-type AAV2, AAV9 and a heparin binding-deficient AAV2 mutant. Such targeted vectors were able to reconstitute expression of δ-sarcoglycan in the heart of adult δ-sarcoglycan knockout mice after systemic gene transfer in vivo, attesting to the therapeutic potential of this approach.

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Acknowledgements

We thank the vector production unit at the German Cancer Research Center for vector preparations. We thank Dr X Xiao (University of Pittsburgh) for providing the pdsAAV-CMV-GFP construct and Dr D Weichenhan and S Schinkel (University of Heidelberg) for providing the murine δ-sarcoglycan cDNA and C Raupp for valuable help. JAK, MT and OM are supported by grants of the Deutsche Forschungsgemeinschaft (KL 516/8-2; TR-448/5-3; Mu 1654/3-2).

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Author notes

  1. Y Ying

    Present address: 4Current address: Department of Clinical Oncology, Hong Kong Cancer Institute and Li Ka Shing Institute of Health Science, Chinese University of Hong Kong, Hong Kong, China,

  2. O J Müller: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Tumorvirology, German Cancer Research Center, Im Neuenheimer Feld 242, Heidelberg, Germany

    Y Ying, B Leuchs & J A Kleinschmidt

  2. University of Heidelberg, Internal Medicine III, Im Neuenheimer Feld 410, Heidelberg, Germany

    O J Müller, C Goehringer & H A Katus

  3. Department of Oncology and Hematology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg, Germany

    M Trepel

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  1. Y Ying
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Correspondence to J A Kleinschmidt.

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Ying, Y., Müller, O., Goehringer, C. et al. Heart-targeted adeno-associated viral vectors selected by in vivo biopanning of a random viral display peptide library. Gene Ther 17, 980–990 (2010). https://doi.org/10.1038/gt.2010.44

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