Aarhus Universitets segl

English

Du er her: AU » Om AU » Organisation » Optimization of Mouse Growth Hormone Plasmid DNA Electrot...

Om AU

Optimization of Mouse Growth Hormone Plasmid DNA Electrotransfer into Tibialis Cranialis Muscle of "Little" Mice

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

DOI

  • Eliana Rosa Lima, Instituto de Pesquisas Energeticas e Nucleares
    • ,
  • Claudia Regina Cecchi, Instituto de Pesquisas Energeticas e Nucleares
    • ,
  • Eliza Higuti, Instituto de Pesquisas Energeticas e Nucleares, Instituto Butantan
    • ,
  • Gustavo Protasio Pacheco de Jesus, Instituto de Pesquisas Energeticas e Nucleares
    • ,
  • Alissandra Moura Gomes, Instituto de Pesquisas Energeticas e Nucleares
    • ,
  • Enio Aparecido Zacarias, Instituto de Pesquisas Energeticas e Nucleares
    • ,
  • Paolo Bartolini, Instituto de Pesquisas Energeticas e Nucleares
    • ,
  • Cibele Nunes Peroni, Instituto de Pesquisas Energeticas e Nucleares

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.

OriginalsprogEngelsk
Artikelnummer5034
TidsskriftMolecules (Basel, Switzerland)
Vol/bind25
Nummer21
Antal sider9
ISSN1420-3049
DOI
StatusUdgivet - okt. 2020

Se relationer på Aarhus Universitet Citationsformater

ID: 200987628