A Novel Homologous Model for Gene Therapy of Dwarfism by Non-Viral Transfer of the Mouse Growth Hormone Gene into Immunocompetent Dwarf Mice

Title:A Novel Homologous Model for Gene Therapy of Dwarfism by Non-Viral Transfer of the Mouse Growth Hormone Gene into Immunocompetent Dwarf Mice

Volume: 14 Issue: 1

Author(s): Claudia R. Cecchi, Eliza Higuti, Nelio A.J. Oliveira, Eliana R. Lima, Maria Jakobsen, Frederick Dagnaes-Hansen, Hanne Gissel, Lars Aagaard, Thomas G. Jensen, Alexander A.L. Jorge, Paolo Bartolini and Cibele N. Peroni

Affiliation:

Keywords: Gene therapy, homologous model, IGF-I, little mice, mouse growth hormone, non-viral gene transfer.

Abstract: 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/10⁶ 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.

Cite this article as:

Cecchi R. Claudia, Higuti Eliza, Oliveira A.J. Nelio, Lima R. Eliana, Jakobsen Maria, Dagnaes-Hansen Frederick, Gissel Hanne, Aagaard Lars, Jensen G. Thomas, Jorge A.L. Alexander, Bartolini Paolo and Peroni N. Cibele, A Novel Homologous Model for Gene Therapy of Dwarfism by Non-Viral Transfer of the Mouse Growth Hormone Gene into Immunocompetent Dwarf Mice, Current Gene Therapy 2014; 14 (1) . https://dx.doi.org/10.2174/1566523214666140224112039