Optimization of mouse growth hormone plasmid DNA electrotransfer into tibialis cranialis muscle of “little” mice

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dc.contributorControle de Qualidadept_BR
dc.contributor.authorLima, Eliana Rosapt_BR
dc.contributor.authorCecchi, Claudia Reginapt_BR
dc.contributor.authorHiguti, Elizapt_BR
dc.contributor.authorJesus, Gustavo Protasio Pacheco dept_BR
dc.contributor.authorGomes, Alissandra Mourapt_BR
dc.contributor.authorZacarias, Enio Aparecidopt_BR
dc.contributor.authorBartolini, Paolopt_BR
dc.contributor.authorPeroni, Cibele Nunespt_BR
dc.date.accessioned2020-11-10T19:55:33Z-
dc.date.accessioned2020-11-10T19:55:38Z-
dc.date.available2020-11-10T19:55:33Z-
dc.date.available2020-11-10T19:55:38Z-
dc.date.issued2020pt_BR
dc.identifier.citationLima ER, Cecchi CR, EH, Jesus GPP, Gomes AM, Zacarias EA, et al. Optimization of mouse growth hormone plasmid DNA electrotransfer into tibialis cranialis muscle of “little” mice. Molecules. 2020 Oct;25(21):5034. doi:10.3390/molecules25215034.pt_BR
dc.identifier.urihttps://repositorio.butantan.gov.br/handle/butantan/3301-
dc.description.abstractPrevious 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.pt_BR
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.format.extent5034pt_BR
dc.language.isoEnglishpt_BR
dc.relation.ispartofMoleculespt_BR
dc.rightsOpen Accesspt_BR
dc.titleOptimization of mouse growth hormone plasmid DNA electrotransfer into tibialis cranialis muscle of “little” micept_BR
dc.typeArticlept_BR
dc.identifier.doi10.3390/molecules25215034pt_BR
dc.identifier.urlhttps://doi.org/10.3390/molecules25215034pt_BR
dc.contributor.externalInstituto de Pesquisas Energéticas e Nucleares (IPEN)pt_BR
dc.contributor.externalAarhus University (AU)pt_BR
dc.identifier.citationvolume25pt_BR
dc.identifier.citationissue21pt_BR
dc.subject.keywordelectrotransferpt_BR
dc.subject.keywordgene therapypt_BR
dc.subject.keywordhomologous modelpt_BR
dc.subject.keywordmIGF-1pt_BR
dc.subject.keywordlittle micept_BR
dc.subject.keywordmouse growth hormonept_BR
dc.subject.keywordnon-viral gene transferpt_BR
dc.subject.keywordtibialis cranialis musclept_BR
dc.relation.ispartofabbreviatedMoleculespt_BR
dc.identifier.citationabntv. 25, n. 21, 5034, out. 2020pt_BR
dc.identifier.citationvancouver2020 Oct;25(21):5034pt_BR
dc.contributor.butantanHiguti, Eliza|:Técnico|:Controle de Qualidadept_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2014/07380-6pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2014/19757-7pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2017/15503-9pt_BR
dc.identifier.bvsccBR78.1pt_BR
dc.identifier.bvsdbIBProdpt_BR
dc.description.dbindexedYespt_BR
item.openairetypeArticle-
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item.grantfulltextopen-
item.languageiso639-1English-
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