Optimization of mouse growth hormone plasmid DNA electrotransfer into tibialis cranialis muscle of "little" mice
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Previous non-viral gene therapy was directed towards two animal models of dwarfism: Immunodeficient (lit/scid) and immunocompetent (lit/lit) dwarf mice. The former, based on hGH DNA administration into muscle, performed better, while the latter, a homologous model based on mGH DNA, was less efficient, though recommended as useful for pre-clinical assays. We have now improved the growth parameters aiming at a complete recovery of the lit/lit phenotype. Electrotransfer was based on three pulses of 375 V/cm of 25 ms each, after mGH-DNA administration into two sites of each non-exposed tibialis cranialis muscle. A 36-day bioassay, performed using 60-day old lit/lit mice, provided the highest GH circulatory levels we have ever obtained for GH non-viral gene therapy: 14.7 ± 3.7 ng mGH/mL. These levels, at the end of the experiment, were 8.5 ± 2.3 ng/mL, i.e., significantly higher than those of the positive control (4.5 ± 1.5 ng/mL). The catch-up growth reached 40.9% for body weight, 38.2% for body length and 82.6%–76.9% for femur length. The catch-up in terms of the mIGF-1 levels remained low, increasing from the previous value of 5.9% to the actual 8.5%. Although a complete phenotypic recovery was not obtained, it should be possible starting with much younger animals and/or increasing the number of injection sites.
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LIMA, ELIANA R.; CECCHI, CLAUDIA R.; HIGUTI, ELIZA; JESUS, GUSTAVO P.P. de; GOMES, ALISSANDRA M.; ZACARIAS, ENIO A.; BARTOLINI, PAOLO; PERONI, CIBELE N. Optimization of mouse growth hormone plasmid DNA electrotransfer into tibialis cranialis muscle of "little" mice. Molecules, v. 25, n. 21, p. 1-9, 2020. DOI: 10.3390/molecules25215034. Disponível em: http://200.136.52.105/handle/123456789/31768. Acesso em: 27 Mar 2026.
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