| Full text | |
| Author(s): |
Lima, Eliana Rosa
;
Cecchi, Claudia Regina
;
Higuti, Eliza
;
Pacheco de Jesus, Gustavo Protasio
;
Gomes, Alissandra Moura
;
Zacarias, Enio Aparecido
;
Bartolini, Paolo
;
Peroni, Cibele Nunes
Total Authors: 8
|
| Document type: | Journal article |
| Source: | Molecules; v. 25, n. 21, p. 9-pg., 2020-11-01. |
| Abstract | |
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. (AU) | |
| 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 Opportunities: | Regular Research Grants |
| 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 Opportunities: | Scholarships in Brazil - Master |
| FAPESP's process: | 17/15503-9 - Gene therapy by electrotransfer of mouse growth hormone gene in an animal model of osteogenesis imperfecta |
| Grantee: | Cibele Nunes Peroni |
| Support Opportunities: | Regular Research Grants |