Institut for Biomedicin

Claudia Cecchi Kaadt

A novel homologous model for gene therapy of dwarfism by non-viral transfer of the mouse growth hormone gene into immunocompetent dwarf mice

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

  • Claudia R Cecchi
  • Eliza Higuti
  • ,
  • Nelio A J Oliveira
  • ,
  • Eliana R Lima, Danmark
  • Maria Jakobsen, Danmark
  • Frederick Dagnaes-Hansen, Danmark
  • Hanne Gissel, Danmark
  • Lars Aagaard
  • Thomas G Jensen
  • Alexander A L Jorge
  • ,
  • Paolo Bartolini
  • ,
  • Cibele N Peroni, Biotechnology Center, IPENCNEN, Avenida Professor Lineu Prestes 2242, Cidade Universitaria, 05508- 000, Sao Paulo, SP, Brazil.

The possibilities for non-viral GH gene therapy are studied in immunocompetent dwarf mice (lit/lit). As expression vector we used a plasmid previously employed in immunodeficient dwarf mice (pUBI-hGH-gDNA) by replacing the human GH gene with the genomic sequence of mouse-GH DNA (pUBI-mGH-gDNA). HEK-293 human cells transfected with pUBI-mGH-gDNA produced 3.0 µg mGH/10(6) cells/day compared to 3.7 µg hGH/106 cells/day for pUBIhGH- gDNA transfected cells. The weight of lit/lit mice treated with the same two plasmids (50 µg DNA/mouse) by electrotransfer into the quadriceps muscle was followed for 3 months. The weight increase up to 15 days for mGH, hGH and saline treated mice were 0.130, 0.112 and 0.027 g/mouse/day. Most sera from hGH-treated mice contained anti-hGH antibodies already on day 15, with the highest titers on day 45, while no significant anti-mGH antibodies were observed in mGH-treated mice. At the end of 3 months, the weight increase for mGH-treated mice was 34.3%, while the nose-to-tail and femur lengths increased 9.5% and 24.3%. Mouse-GH and hGH circulating levels were 4-5 ng/mL 15 days after treatment, versus control levels of ~0.7 ng GH/mL (P<0.001). In mGH-treated mice, mIGF-I determined on days 15, 45 and 94 were 1.5- to 3-fold higher than the control and 1.2- to 1.6-fold higher than hGH-treated mice. The described homologous model represents an important progress forming the basis for preclinical testing of non-viral gene therapy for GH deficiency.

TidsskriftCurrent Gene Therapy
Sider (fra-til)44-51
Antal sider8
StatusUdgivet - feb. 2014

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