CLAUDIA REGINA CECCHI
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Artigo IPEN-doc 27539 Optimization of mouse growth hormone plasmid DNA electrotransfer into tibialis cranialis muscle of "little" mice2020 - LIMA, ELIANA R.; CECCHI, CLAUDIA R.; HIGUTI, ELIZA; JESUS, GUSTAVO P.P. de; GOMES, ALISSANDRA M.; ZACARIAS, ENIO A.; BARTOLINI, PAOLO; PERONI, CIBELE N.Previous non-viral gene therapy was directed towards two animal models of dwarfism: Immunodeficient (lit/scid) and immunocompetent (lit/lit) dwarf mice. The former, based on hGH DNA administration into muscle, performed better, while the latter, a homologous model based on mGH DNA, was less efficient, though recommended as useful for pre-clinical assays. We have now improved the growth parameters aiming at a complete recovery of the lit/lit phenotype. Electrotransfer was based on three pulses of 375 V/cm of 25 ms each, after mGH-DNA administration into two sites of each non-exposed tibialis cranialis muscle. A 36-day bioassay, performed using 60-day old lit/lit mice, provided the highest GH circulatory levels we have ever obtained for GH non-viral gene therapy: 14.7 ± 3.7 ng mGH/mL. These levels, at the end of the experiment, were 8.5 ± 2.3 ng/mL, i.e., significantly higher than those of the positive control (4.5 ± 1.5 ng/mL). The catch-up growth reached 40.9% for body weight, 38.2% for body length and 82.6%–76.9% for femur length. The catch-up in terms of the mIGF-1 levels remained low, increasing from the previous value of 5.9% to the actual 8.5%. Although a complete phenotypic recovery was not obtained, it should be possible starting with much younger animals and/or increasing the number of injection sites.Artigo IPEN-doc 24222 Efficient non-invasive plasmid-DNA administration into tibialis cranialis muscle of “little” mice2017 - CECCHI, C.R.; HIGUTI, E.; LIMA, E.R.; VIEIRA, D.P.; SQUAIR, P.L.; PERONI, C.N.; BARTOLINI, P.Background: An alternative treatment for growth hormone deficiency based on hGH-DNA administration, followed by electro gene transfer, was investigated by injecting the plasmid into surgically exposed or non-exposed quadriceps or tibialis muscle of immunodeficient “little” mice. Methods: An optimization of electrotransfer conditions via a new combination of high/low voltage pulses is presented. After 3 days, serum hGH was determined and in a 28-day assay, the relative growth parameters were compared. Results: Both groups exhibited similar results: 5.0 ± 2.2 (SD) and 3.5 ± 0.9 ng hGH/ml (P>0.05; n=7) for the exposed quadriceps and non-exposed tibialis treatments, respectively. The final body weight increases were 16.1% for the quadriceps and 18.9% for the tibialis group. The tail and nose-to-tail length increases were 4.5% and 7.1% for the quadriceps and 4.8 and 4.6% for the tibialis group. The right and left femur length increases, obtained from radiographic measurements, were 16.9% and 12.7% for the quadriceps and 19.4% and 12.3% for the tibialis, respectively. A non-significant difference between exposed quadriceps and non-exposed tibialis treatments (P=0.48) was confirmed via a completely integrated statistical analysis. Circulating mIGF-1 levels were 126 ± 47, 106 ± 93 (P>0.05) and 38 ± 15 ng/ml for the quadriceps, tibialis and saline treatments, respectively. Conclusion: These results show that hGH-DNA administration into non-exposed tibialis muscle followed by the new HV/LV electrotransfer protocol was an equally efficient, less traumatic treatment,Resumo IPEN-doc 22302 Efficient and non-invasive plasmid DNA administration into the tibialis cranialis muscle of dwarf mice2014 - HIGUTI, ELIZA; CECCHI, CLAUDIA R.; LIMA, ELIANA R.; AZEVEDO, MAYARA L. de; AAGAARD, LARS; BARTOLINI, PAOLO; PERONI, CIBELE N.Artigo IPEN-doc 21730 Partial correction of the dwart phenotype by non-viral transfer of the growth hormone gene in mice: treatment age is critical2016 - 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.Capítulo IPEN-doc 21588 Modelos de terapia gênica baseados na expressão de hormônio de crescimento em células humanas e na administração de DNA plasmidial em camundongos anões2015 - PERONI, CIBELE N.; CECCHI, CLAUDIA R.; HIGUTI, ELIZA; BARTOLINI, PAOLOResumo IPEN-doc 21241 Early treatment for growth hormone deficiency based on naked DNA administration in dwart mice allows efficient catch-up growth2015 - HIGUTI, ELIZA; CECCHI, CLAUDIA R.; LIMA, ELIANA R.; AAGAARD, LARS; JENSEN, THOMAS G.; BARTOLINI, PAOLO; PERONI, CIBELE N.Capítulo IPEN-doc 17391 Different ex vivo and direct in vivo DNA administration strategies for growth hormone gene therapy in dwarf animals2011 - PERONI, CIBELE N.; OLIVEIRA, NELIO A. de J.; CECCHI, CLAUDIA R.; HIGUTI, ELIZA; BARTOLINI, PAOLOResumo IPEN-doc 17505 In vitro, ex vivo and in vivo recombinant growth hormone synthesis, for gene therapy applications2011 - PERONI, CIBELE N.; OLIVEIRA, NELIO A. de J.; CECCHI, CLAUDIA R.; HIGUTI, ELIZA; SILVA, JULIANA T. da; JORGE, ALEXANDER A. de L.; JENSEN, THOMAS G.; BARTOLINI, PAOLOResumo IPEN-doc 17526 Growth parameters after intramuscular hGH plasmid administration compared to recombinant hGH injections in LIT/SCID mice2011 - HIGUTI, E.; CECCHI, C.R.; OLIVEIRA, N.A.J.; SILVA, J.T.; JORGE, A.A.L.; BARTOLINI, P.; PERONI, C.N.Resumo IPEN-doc 17367 Non-viral gene transfer to skin, muscle and liver for expression of growth homone2011 - CECCHI, CLAUDIA R.; DAGUACS HANSEN, FREDERIK; AGAARD, LARS; GISSEL, HANNE; GOTHELF, ANITA; JAKOBSEN, MARIA; HANSEN, BIRGIT H.; FRYSTYK, JAN; OLIVEIRA, NELIO A.J.; HIGUTI, ELIZA; BARTOLINI, PAOLO; PERONI, CIBELE N.; JENSEN, THOMAS G.
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