Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSPHIGUTI, ElizaCECCHI, Claudia R.OLIVEIRA, Nelio A. J.VIEIRA, Daniel P.JENSEN, Thomas G.JORGE, Alexander A. L.BARTOLINI, PaoloPERONI, Cibele N.2013-07-302013-07-302012CURRENT GENE THERAPY, v.12, n.6, p.437-443, 20121566-5232https://observatorio.fm.usp.br/handle/OPI/514In 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.engrestrictedAccesshuman growth hormoneimmunodeficient little micemouse insulin-like growth factor Inaked DNAhormone-releasing-hormonephase-i trialprimary human keratinocyteslong-term growthgene-therapyhypophysectomized miceanimal-modelexpressionelectroporationdeficiencyarticleCopyright BENTHAM SCIENCE PUBL LTD10.2174/156652312803519797Genetics & Heredity