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1 Department of Human Genetics, University of Aarhus, Aarhus, Denmark
2 Department of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark
3 Medical Research Laboratories and Medical Department of Diabetes and Endocrinology, Aarhus University Hospital, Aarhus, Denmark
* To whom correspondence should be addressed. E-mail: thomas{at}humgen.au.dk.
Non-viral gene transfer was investigated as a potential treatment of growth hormone deficiency (GHD) using hypophysectomized mice as a model. Following a single hydrodynamic administration of naked plasmid DNA containing the human growth hormone (hGH) gene controlled by an ubiquitin promoter, sustained elevation of circulating hGH was observed the entire observation period (68 days), with a concomitant normalisation of circulating insulin-like growth factor I (IGF-I) and IGF binding protein 3 (IGFBP-3). Further, longitudinal growth was corrected in terms of normalization of tibia length, tail length and body weight gain. Liver, spleen and lung weights were normalized, while heart weight was partly normalized. hGH mRNA was exclusively expressed in liver tissue. In conclusion, we showed that non-viral hGH gene transfer normalises longitudinal growth in hypophysectomized mice, indicating that this method potentially could be relevant as a new therapeutic tool in the clinical handling of GHD.
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