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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.)

Partial correction of the dwarf phenotype by non-viral transfer of the growth hormone gene in mice: Treatment age is critical

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Author(s):
Higuti, Eliza [1] ; Cecchi, Claudia R. [1, 2] ; Oliveira, Nelio A. J. [1, 3] ; Lima, Eliana R. [1] ; Vieira, Daniel P. [1] ; Aagaard, Lars [2] ; Jensen, Thomas G. [2] ; Jorge, Alexander A. L. [4] ; Bartolini, Paolo [1] ; Peroni, Cibele N. [1]
Total Authors: 10
Affiliation:
[1] CNEN, IPEN, Ctr Biotechnol, Cidade Univ, Ave Prof Lineu Prestes 2242, BR-05508900 Sao Paulo, SP - Brazil
[2] Aarhus Univ, Dept Biomed, DK-8000 Aarhus - Denmark
[3] Univ Minnesota, Lillehei Heart Inst, Minneapolis, MN - USA
[4] Univ Sao Paulo, Sch Med, FMUSP, Genet Endocrinol Unit LIM25, Endocrinol Dept, Sao Paulo, SP - Brazil
Total Affiliations: 4
Document type: Journal article
Source: GROWTH HORMONE & IGF RESEARCH; v. 26, p. 1-7, FEB 2016.
Web of Science Citations: 2
Abstract

Non-viral transfer of the growth hormone gene to different muscles of immunodeficient dwarf (lit/scid) mice is under study with the objective of improving phenotypic correction via this particular gene therapy approach. Plasmid DNA was administered into the exposed quadriceps or non-exposed tibialis cranialis muscle of lit/scid mice followed by electroporation, monitoring several growth parameters. In a 6-month bioassay, 50 pg DNA were injected three times into the quadriceps muscle of 80-day old mice. A 50% weight increase, with a catch-up growth of 21%, together with a 16% increase for nose-to-tail and tail lengths (catch-up = 19-21%) and a 24-28% increase for femur length (catch-up = 53-60%), were obtained. mIGF1 serum levels were similar to 7-fold higher than the basal levels for untreated mice, but still similar to 2-fold lower than in non-dwarf scid mice. Since treatment age was found to be particularly important in a second bioassay utilizing 40-day old mice, these pubertal mice were compared in a third bioassay with adult (80-day old) mice, all treated twice with 50 mu g DNA injected into each tibialis cranialis muscle, via a less invasive approach. mIGF1 concentrations at the same level as co-aged scid mice were obtained 15 days after administration in pubertal mice. Catch-up growth, based on femur length (77%), nose-to-tail (36%) and tail length (39%) increases was 40 to 95% higher than those obtained upon treating adult mice. These data pave the way for the development of more effective pre-clinical assays in pubertal dwarf mice for the treatment of GH deficiency via plasmid-DNA muscular administration. (C) 2015 Elsevier Ltd. All rights reserved. (AU)

FAPESP's process: 14/04277-0 - Growth Hormone Gene therapy: homologous treatment based on plasmid DNA administration and on microencapsulated cells implanted in immunocompetent dwarf mice (lit/lit)
Grantee:Cláudia Regina Cecchi
Support type: Scholarships abroad - Research Internship - Post-doctor
FAPESP's process: 14/19757-7 - Growth hormone gene therapy: plasmid DNA injection and microencapsulated cells implantation in dwarf mice
Grantee:Cibele Nunes Peroni
Support type: Regular Research Grants
FAPESP's process: 14/18242-3 - Gene therapy for growth hormone deficiency mediated by minicircle DNA electrotransfer in dwarf mice
Grantee:Eliza Higuti Sousa
Support type: Scholarships abroad - Research Internship - 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
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: 14/07380-6 - Optimization of in vivo growth hormone gene transfer parameters for phenotypic correction of dwarf mice
Grantee:Eliana Rosa Lima Filha
Support type: Scholarships in Brazil - Master