Complete phenotypic correction of dwarfism by injection of plasmid DNA in an animal model of isolated growth hormone deficiency

• Grant number: 11/21708-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): January 01, 2012
• Effective date (End): January 02, 2016
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Cibele Nunes Peroni
• Grantee: Eliza Higuti Sousa
• Host Institution: Instituto de Pesquisas Energéticas e Nucleares (IPEN). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São Paulo , SP, Brazil
• Associated scholarship(s): 14/18242-3 - Gene therapy for growth hormone deficiency mediated by minicircle DNA electrotransfer in dwarf mice, BE.EP.DR

Abstract

Gene therapy for human growth hormone (hGH) is a promising method and has the great advantage of replacing the entire pharmaceutical control and production processes of this protein, eliminating the drawbacks of the standard treatment, and can provide a release of GH in a more similar manner to the natural process. Our research group, in the Biotechnology Center of IPEN, develops several works related to gene therapy of human growth hormone (hGH) and murine growth hormone (mGH). And now we consider to be most promising methodology, used by our group, the direct injection of plasmid DNA containing the gene for hGH, followed by electroporation, into dwarf and immunodeficient mice (lit/scid), whose characteristics are very similar to GH deficiency in humans(GHD). This methodology provided continuous secretion of hGH for at least 60 days of treatment, and a partial phenotypic correction of dwarfism with weight increase of approximately 30% besides a slope of the growth curve identical to that of the standard treatment with daily injections of recombinant human growth hormone (r-hGH) in a subsequent assay of 28 days. The proposal for this project is to conduct a long duration assay (or assays), in which full phenotypic correction of dwarfism in this animal model of isolated GH deficiency can be achieved. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

HIGUTI, ELIZA; CECCHI, CLAUDIA R.; OLIVEIRA, NELIO A. J.; VIEIRA, DANIEL P.; JENSEN, THOMAS G.; JORGE, ALEXANDER A. L.; BARTOLINI, PAOLO; PERONI, CIBELE N.. Growth Responses Following a Single Intra-Muscular hGH Plasmid Administration Compared to Daily Injections of hGH in Dwarf Mice. CURRENT GENE THERAPY, v. 12, n. 6, p. 437-443, DEC 2012. (11/21708-6)

CECCHI, CLAUDIA R.; HIGUTI, ELIZA; OLIVEIRA, NELIO A. J.; LIMA, ELIANA R.; JAKOBSEN, MARIA; DAGNAES-HANSEN, FREDERICK; GISSEL, HANNE; AAGAARD, LARS; JENSEN, THOMAS G.; JORGE, ALEXANDER A. L.; et al. 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, v. 14, n. 1, p. 44-51, FEB 2014. (11/21708-6, 11/23365-9, 13/03747-0)

HIGUTI, ELIZA; CECCHI, CLAUDIA R.; OLIVEIRA, NELIO A. J.; LIMA, ELIANA R.; VIEIRA, DANIEL P.; AAGAARD, LARS; JENSEN, THOMAS G.; JORGE, ALEXANDER A. L.; BARTOLINI, PAOLO; PERONI, CIBELE N.. Partial correction of the dwarf phenotype by non-viral transfer of the growth hormone gene in mice: Treatment age is critical. GROWTH HORMONE & IGF RESEARCH, v. 26, p. 1-7, FEB 2016. (14/04277-0, 14/18242-3, 13/03747-0, 11/21708-6, 14/19757-7, 14/07380-6)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SOUSA, Eliza Higuti. Phenotypic correction of dwarfism mediated by different growth parameters after plasmid DNA administration in an animal model of isolated growth hormone deficiency. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Pesquisas Energéticas e Nucleares (IPEN/BT) São Paulo.