Physiological effects of human growth hormone produced after hydrodynamic gene transfer of a plasmid vector containing the human ubiquitin promotor.
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.
Dagnaes-Hansen
Frederik
F
Department of Medical Microbiology and Immunology, University of Aarhus, 8000 Aarhus C, Denmark.
Holst
Henrik U
HU
Søndergaard
Morten
M
Vorup-Jensen
Thomas
T
Flyvbjerg
Allan
A
Jensen
Uffe B
UB
Jensen
Thomas G
TG
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
D000906:Antibodies; D025801:Ubiquitin; D013006:Growth Hormone