Growth Responses Following a Single Intra-Muscular hGH Plasmid Administration Compared to Daily Injections of hGH in Dwarf Mice
Claudia R. Cecchi,
Nelio A.J. Oliveira,
Daniel P. Vieira,
Thomas G. Jensen,
Alexander A.L. Jorge,
Cibele N. Peroni.
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 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.
Keywords: Electroporation, gene therapy, human growth hormone, immunodeficient little mice, mouse insulin-like growth
factor I, naked DNA, electroporation, gene therapy, human growth hormone, immunodeficient little mice, mouse insulin growth factor I, naked DNA, electroporation methodology, cachexia
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