Progress in gene therapy has hinted at the potential misuse of gene transfer in sports to achieve better athletic performance, while escaping from traditional doping detection methods. Suitable animal models are therefore required in order to better define the potential effects and risks of gene doping. Here we describe a mouse model of gene doping based on adeno-associated virus (AAV)-mediated delivery of the insulin-like growth factor-I (IGF-I) cDNA to multiple muscles. This treatment determined marked muscle hypertrophy, neovascularization, and fast-to-slow fiber type transition, similar to endurance exercise. In functional terms, treated mice showed impressive endurance gain, as determined by an exhaustive swimming test. The proteomic profile of the transduced muscles at 15 and 30 days after gene delivery revealed induction of key proteins controlling energy metabolism. At the earlier time point, enzymes controlling glycogen mobilization and anaerobic glycolysis were induced, whereas they were later replaced by proteins required for aerobic metabolism, including enzymes related to the Krebs cycle and oxidative phosphorylation. These modifications coincided with the induction of several structural and contractile proteins, in agreement with the observed histological and functional changes. Collectively, these results give important insights into the biological response of muscles to continuous IGF-I expression in vivo and warn against the potential misuse of AAV-IGF1 as a doping agen

Enhanced athletic performance upon multi-site AAV-IGF1 gene transfer coincides with massive modification of the muscle proteome / A. Macedo, M. Moriggi, M. Vasso, S. De Palma, M. Sturnega, G. Friso, C. Gelfi, M. Giacca, S. Zacchigna. - In: HUMAN GENE THERAPY. - ISSN 1043-0342. - 23:2(2012 Feb), pp. 146-157.

Enhanced athletic performance upon multi-site AAV-IGF1 gene transfer coincides with massive modification of the muscle proteome

M. Moriggi;M. Vasso;C. Gelfi;
2012-02

Abstract

Progress in gene therapy has hinted at the potential misuse of gene transfer in sports to achieve better athletic performance, while escaping from traditional doping detection methods. Suitable animal models are therefore required in order to better define the potential effects and risks of gene doping. Here we describe a mouse model of gene doping based on adeno-associated virus (AAV)-mediated delivery of the insulin-like growth factor-I (IGF-I) cDNA to multiple muscles. This treatment determined marked muscle hypertrophy, neovascularization, and fast-to-slow fiber type transition, similar to endurance exercise. In functional terms, treated mice showed impressive endurance gain, as determined by an exhaustive swimming test. The proteomic profile of the transduced muscles at 15 and 30 days after gene delivery revealed induction of key proteins controlling energy metabolism. At the earlier time point, enzymes controlling glycogen mobilization and anaerobic glycolysis were induced, whereas they were later replaced by proteins required for aerobic metabolism, including enzymes related to the Krebs cycle and oxidative phosphorylation. These modifications coincided with the induction of several structural and contractile proteins, in agreement with the observed histological and functional changes. Collectively, these results give important insights into the biological response of muscles to continuous IGF-I expression in vivo and warn against the potential misuse of AAV-IGF1 as a doping agen
GROWTH-FACTOR-I ; DIFFERENCE GEL-ELECTROPHORESIS ; RECOMBINANT ADENOASSOCIATED VIRUS ; MURINE C2C12 MYOBLASTS ; FACTOR IGF-I ; SKELETAL-MUSCLE ; MEDIATED EXPRESSION ; EXPERIMENTAL-DESIGN ; RAT MUSCLE ; INSULIN
Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica
Article (author)
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/165911
Citazioni
  • ???jsp.display-item.citation.pmc??? 4
  • Scopus 17
  • ???jsp.display-item.citation.isi??? 15
social impact