title: Physiological effects of human growth hormone produced after hydrodynamic gene transfer of a plasmid vector containing the human ubiquitin promotor.
abstract: Human growth hormone (hGH) deficiency causes retarded growth and abnormalities in body fat distribution and abundance, muscle growth, and bone mineralization. While injection of recombinant hGH may reverse or ameliorate symptoms of deficiency, therapy aiming at in vivo synthesis of hGH is still of considerable clinical interest. Hydrodynamic injection of a simple plasmid vector containing a human ubiquitin promotor and the hGH gene were found to result in high and prolonged expression. Synthesis of hGH was achieved both in NOD/SCID mice and in three different inbred strains of immune competent mice. Although hGH antibodies were produced in immunocompetent mice, physiological effects of the protein were documented by increase in body weight, increased serum levels of insulin-like growth factor I and relative increased weight of the internal organs. Nonviral gene therapy may be regarded as a potential future way of reconstituting hGH expression in deficient individuals.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Aarhus, 8000 Aarhus C, Denmark.
authors.forename: Frederik
authors.initials: F
authors.lastname: Dagnaes-Hansen
authors.forename: Henrik U
authors.initials: HU
authors.lastname: Holst
authors.forename: Morten
authors.initials: M
authors.lastname: Søndergaard
authors.forename: Thomas
authors.initials: T
authors.lastname: Vorup-Jensen
authors.forename: Allan
authors.initials: A
authors.lastname: Flyvbjerg
authors.forename: Uffe B
authors.initials: UB
authors.lastname: Jensen
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Jensen
mesh_terms: D000818:Animals; D017849:Animals, Inbred Strains; D000906:Antibodies / Q000276:immunology; D016503:Drug Delivery Systems; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D013006:Growth Hormone / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007121:Immunocompetence; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics*; D011401:Promoter Regions, Genetic; D025801:Ubiquitin / Q000235:genetics
chemical_list: D000906:Antibodies; D025801:Ubiquitin; D013006:Growth Hormone