Growth Hormone Gene therapy: homologous treatment based on plasmid DNA administration and on microencapsulated cells implanted in immunocompetent dwarf mice (lit/lit)

• Grant number: 14/04277-0
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date until: April 01, 2014
• End date until: March 31, 2015
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Cibele Nunes Peroni
• Grantee: Claudia Regina Cecchi
• Supervisor: Lars Aagaard
• Host Institution: Instituto de Pesquisas Energéticas e Nucleares (IPEN). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São Paulo , SP, Brazil
• Institution abroad: Aarhus University, Denmark
• Associated to the scholarship: 13/03747-0 - Growth hormone gene therapy: homologous treatment with plasmid DNA and with implant of microencapsulated cells in immunocompetent dwarf mice (lit/lit), BP.PD

Abstract

In previous work we have demonstrated significant phenotypic effects in immunodeficient mice dwarfs obtained upon administration of plasmid DNA containing the growth hormone gene (GH) , followed by electroporation . These effects were also comparable to those obtained by repeated injections of recombinant hormone in the same animals . In this project , in order to get closer to preclinical models , we aim to: a) continue the research already undertaken in relation to homologous models of gene therapy in immunocompetent mice that were treated with the mouse GH gene (mGH ) compared with human (hGH ), B) to implant in the same lit/lit mice human retinal microencapsulated epithelial cells, transfected by a transposon and expressing hGH or mGH. In the first case , based on the data already submitted by the candidate ( PhD thesis ) electroporation protocol modified to do not exposure the muscle, using a combination of high and low pulses. Also the construction of vectors that enable greater levels of circulating IGF-I, in analogy to the conditions for treatment to children with GH deficiency. In the second case an alternative technique, where human epithelial cells already utilized in clinical cell therapy protocols will be used for the first time in a model to the treatment of GH deficiency will be developed. (AU)

Scientific publications

(4)

(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)

CECCHI, CLAUDIA R.; ALSING, SIDSEL; JESUS, GUSTAVO P. P.; ZACARIAS, ENIO A.; KJAER, LISBETH; CLEMENT, MICHELLE S.; KUMAGAI-BRAESCH, MAKIKO; CORYDON, THOMAS J.; BARTOLINI, PAOLO; PERONI, CIBELE N.; et al. Sustained secretion of human growth hormone from TheraCyte devices encapsulated with PiggyBac-engineered retinal pigment epithelium cells. TISSUE & CELL, v. 82, p. 13-pg., 2023-06-01. (13/03747-0, 14/19757-7, 14/07380-6, 14/04277-0, 14/18242-3)

CECCHI, C. R.; HIGUTI, E.; LIMA, E. R.; VIEIRA, D. P.; SQUAIR, P. L.; PERONI, C. N.; BARTOLINI, P.. Efficient Non-Invasive Plasmid-DNA Administration into Tibialis Cranialis Muscle of "Little" Mice. CURRENT MOLECULAR MEDICINE, v. 17, n. 3, p. 6-pg., 2017-01-01. (13/03747-0, 14/19757-7, 14/07380-6, 14/04277-0, 14/18242-3)

CECCHI, C. R.; HIGUTI, E.; LIMA, E. R.; VIEIRA, D. P.; SQUAIR, P. L.; PERONI, C. N.; BARTOLINI, P.. Efficient Non-Invasive Plasmid-DNA Administration into Tibialis Cranialis Muscle of ``Little{''} Mice. CURRENT MOLECULAR MEDICINE, v. 17, n. 3, p. 230-235, 2017. (14/19757-7, 14/07380-6, 14/04277-0, 14/18242-3, 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)