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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Cecchi, Claudia R. [1] ; Higuti, Eliza [1] ; Oliveira, Nelio A. J. [1] ; Lima, Eliana R. [1] ; Jakobsen, Maria [2] ; Dagnaes-Hansen, Frederick [2] ; Gissel, Hanne [2] ; Aagaard, Lars [2] ; Jensen, Thomas G. [2] ; Jorge, Alexander A. L. [3] ; Bartolini, Paolo [1] ; Peroni, Cibele N. [1]
Total Authors: 12
[1] Inst Pesquisas Energet & Nucl IPEN CNEN, Ctr Biotechnol, Sao Paulo - Brazil
[2] Aarhus Univ, Dept Biomed, DK-8000 Aarhus C - Denmark
[3] Univ Sao Paulo, Sch Med FMUSP, Dept Endocrinol, Genet Endocrinol Unit LIM25, Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Source: CURRENT GENE THERAPY; v. 14, n. 1, p. 44-51, FEB 2014.
Web of Science Citations: 6

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 mu g mGH/10(6) cells/day compared to 3.7 mu g hGH/10(6) cells/day for pUBI-hGH-gDNA transfected cells. The weight of lit/lit mice treated with the same two plasmids (50 mu g 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 similar to 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. (AU)

FAPESP's process: 11/23365-9 - Electrotransfer of a plasmid containing the gene for murine growth hormone in dwarf mice to the obtainment of a homologous model of in vivo gene therapy
Grantee:Eliana Rosa Lima Filha
Support type: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 13/03747-0 - Growth Hormone Gene Therapy: homologous treatment with plasmid DNA and with implant of microencapsulated cells in immunocompetent dwarf mice (lit/lit)
Grantee:Cláudia Regina Cecchi
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 11/21708-6 - Complete phenotypic correction of dwarfism by injection of plasmid DNA in an animal model of isolated growth hormone deficiency
Grantee:Eliza Higuti Sousa
Support type: Scholarships in Brazil - Doctorate