Growth Responses Following a Single Intra-Muscular hGH Plasmid Administration Compared to Daily Injections of hGH in Dwarf Mice
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Citações na Scopus
5
Tipo de produção
article
Data de publicação
2012
Título da Revista
ISSN da Revista
Título do Volume
Editora
BENTHAM SCIENCE PUBL LTD
Autores
HIGUTI, Eliza
CECCHI, Claudia R.
OLIVEIRA, Nelio A. J.
VIEIRA, Daniel P.
JENSEN, Thomas G.
BARTOLINI, Paolo
PERONI, Cibele N.
Citação
CURRENT GENE THERAPY, v.12, n.6, p.437-443, 2012
Resumo
In previous work, sustained levels of circulating human growth hormone (hGH) and a highly significant weight increase were observed after electrotransfer of naked plasmid DNA (hGH-DNA) into the muscle of immunodeficient dwarf mice (lit/scid). In the present study, the efficacy of this in vivo gene therapy strategy is compared to daily injections (5 mu g/twice a day) of recombinant hGH (r-hGH) protein, as assessed on the basis of several growth parameters. The slopes of the two growth curves were found to be similar (P>0.05): 0.095 g/mouse/d for protein and 0.094 g/mouse/d for DNA injection. In contrast, the weight increases averaged 35.5% (P<0.001) and 23.1% (P<0.01) for protein and DNA administration, respectively, a difference possibly related to the electroporation methodology. The nose-to-tail linear growth increases were 15% and 9.6% for the protein and DNA treatments, respectively, but mouse insulin-like growth factor I (mIGF-I) showed a greater increase over the control with DNA (5- to 7-fold) than with protein (3- to 4-fold) administration. The weight increases of several organs and tissues (kidneys, spleen, liver, heart, quadriceps and gastrocnemius muscles) were 1.3- to 4.6-fold greater for protein than for DNA administration, which gave a generally more proportional growth. Glucose levels were apparently unaffected, suggesting the absence of effects on glucose tolerance. A gene transfer strategy based on a single hGH-DNA administration thus appears to be comparable to repeated hormone injections for promoting growth and may represent a feasible alternative for the treatment of growth hormone deficiency.
Palavras-chave
human growth hormone, immunodeficient little mice, mouse insulin-like growth factor I, naked DNA
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