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AAV-mediated in vivo functional selection of tissue-protective factors against ischaemia

Author

Listed:
  • Giulia Ruozi

    (Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB))

  • Francesca Bortolotti

    (Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB))

  • Antonella Falcione

    (Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB))

  • Matteo Dal Ferro

    (Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB)
    Surgical and Health Sciences, University of Trieste)

  • Laura Ukovich

    (Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB))

  • Antero Macedo

    (Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB))

  • Lorena Zentilin

    (Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB))

  • Nicoletta Filigheddu

    (University of Piemonte Orientale ‘A. Avogadro’)

  • Gianluca Gortan Cappellari

    (Surgical and Health Sciences, University of Trieste)

  • Giovanna Baldini

    (Surgical and Health Sciences, University of Trieste)

  • Marina Zweyer

    (Surgical and Health Sciences, University of Trieste)

  • Rocco Barazzoni

    (Surgical and Health Sciences, University of Trieste)

  • Andrea Graziani

    (University of Piemonte Orientale ‘A. Avogadro’)

  • Serena Zacchigna

    (Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB)
    Surgical and Health Sciences, University of Trieste)

  • Mauro Giacca

    (Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB)
    Surgical and Health Sciences, University of Trieste)

Abstract

Functional screening of expression libraries in vivo would offer the possibility of identifying novel biotherapeutics without a priori knowledge of their biochemical function. Here we describe a procedure for the functional selection of tissue-protective factors based on the in vivo delivery of arrayed cDNA libraries from the mouse secretome using adeno-associated virus (AAV) vectors. Application of this technique, which we call FunSel, in the context of acute ischaemia, revealed that the peptide ghrelin protects skeletal muscle and heart from ischaemic damage. When delivered to the heart using an AAV9 vector, ghrelin markedly reduces infarct size and preserves cardiac function over time. This protective activity associates with the capacity of ghrelin to sustain autophagy and remove dysfunctional mitochondria after myocardial infarction. Our findings describe an innovative tool to identify biological therapeutics and reveal a novel role of ghrelin as an inducer of myoprotective autophagy.

Suggested Citation

  • Giulia Ruozi & Francesca Bortolotti & Antonella Falcione & Matteo Dal Ferro & Laura Ukovich & Antero Macedo & Lorena Zentilin & Nicoletta Filigheddu & Gianluca Gortan Cappellari & Giovanna Baldini & M, 2015. "AAV-mediated in vivo functional selection of tissue-protective factors against ischaemia," Nature Communications, Nature, vol. 6(1), pages 1-15, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8388
    DOI: 10.1038/ncomms8388
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    Cited by:

    1. Toshiyuki Ko & Seitaro Nomura & Shintaro Yamada & Kanna Fujita & Takanori Fujita & Masahiro Satoh & Chio Oka & Manami Katoh & Masamichi Ito & Mikako Katagiri & Tatsuro Sassa & Bo Zhang & Satoshi Hatsu, 2022. "Cardiac fibroblasts regulate the development of heart failure via Htra3-TGF-β-IGFBP7 axis," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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