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

Giulia Ruozi; Francesca Bortolotti; Antonella Falcione; Matteo Dal Ferro; Laura Ukovich; Antero MacEdo; Lorena Zentilin; Nicoletta Filigheddu; Gianluca Gortan Cappellari; Giovanna Baldini; Marina Zweyer; Rocco Barazzoni; Andrea Graziani; Serena Zacchigna; Mauro Giacca

doi:10.1038/ncomms8388

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

Giulia Ruozi, Francesca Bortolotti, Antonella Falcione, Matteo Dal Ferro, Laura Ukovich, Antero MacEdo, Lorena Zentilin, Nicoletta Filigheddu, Gianluca Gortan Cappellari, Giovanna Baldini, Marina Zweyer, Rocco Barazzoni, Andrea Graziani, Serena Zacchigna, Mauro Giacca^*

^*Corresponding author for this work

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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.

Original language	English
Article number	7388
Journal	Nature Communications
Volume	6
Issue number	1
Early online date	11 Jun 2015
DOIs	https://doi.org/10.1038/ncomms8388
Publication status	Published - 11 Jun 2015

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AAV-mediated in vivo_RUOZI_Acc5May2016Epub11Jun2015_GOLD VoR (CC BY)Final published version, 2.51 MBLicence: CC BY

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Ruozi, G., Bortolotti, F., Falcione, A., Dal Ferro, M., Ukovich, L., MacEdo, A., Zentilin, L., Filigheddu, N., Cappellari, G. G., Baldini, G., Zweyer, M., Barazzoni, R., Graziani, A., Zacchigna, S., & Giacca, M. (2015). AAV-mediated in vivo functional selection of tissue-protective factors against ischaemia. Nature Communications, 6(1), Article 7388. https://doi.org/10.1038/ncomms8388

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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.",

author = "Giulia Ruozi and Francesca Bortolotti and Antonella Falcione and {Dal Ferro}, Matteo and Laura Ukovich and Antero MacEdo and Lorena Zentilin and Nicoletta Filigheddu and Cappellari, {Gianluca Gortan} and Giovanna Baldini and Marina Zweyer and Rocco Barazzoni and Andrea Graziani and Serena Zacchigna and Mauro Giacca",

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Ruozi, G, Bortolotti, F, Falcione, A, Dal Ferro, M, Ukovich, L, MacEdo, A, Zentilin, L, Filigheddu, N, Cappellari, GG, Baldini, G, Zweyer, M, Barazzoni, R, Graziani, A, Zacchigna, S & Giacca, M 2015, 'AAV-mediated in vivo functional selection of tissue-protective factors against ischaemia', Nature Communications, vol. 6, no. 1, 7388. https://doi.org/10.1038/ncomms8388

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AU - MacEdo, Antero

AU - Zentilin, Lorena

AU - Filigheddu, Nicoletta

AU - Cappellari, Gianluca Gortan

AU - Baldini, Giovanna

AU - Zweyer, Marina

AU - Barazzoni, Rocco

AU - Graziani, Andrea

AU - Zacchigna, Serena

AU - Giacca, Mauro

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

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