{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:20:19Z","timestamp":1760239219964,"version":"build-2065373602"},"reference-count":23,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2020,10,30]],"date-time":"2020-10-30T00:00:00Z","timestamp":1604016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda&amp;#x00E7;&amp;#x00E3;o de Amparo &amp;#x00E0; Pesquisa do Estado de S&amp;#x00E3;o Paulo","award":["2014\/07380-6; 2014\/19757-7; 2017\/15503-9"],"award-info":[{"award-number":["2014\/07380-6; 2014\/19757-7; 2017\/15503-9"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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 \u00b1 3.7 ng mGH\/mL. These levels, at the end of the experiment, were 8.5 \u00b1 2.3 ng\/mL, i.e., significantly higher than those of the positive control (4.5 \u00b1 1.5 ng\/mL). The catch-up growth reached 40.9% for body weight, 38.2% for body length and 82.6%\u201376.9% 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.<\/jats:p>","DOI":"10.3390\/molecules25215034","type":"journal-article","created":{"date-parts":[[2020,10,30]],"date-time":"2020-10-30T00:21:06Z","timestamp":1604017266000},"page":"5034","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Optimization of Mouse Growth Hormone Plasmid DNA Electrotransfer into Tibialis Cranialis Muscle of \u201cLittle\u201d Mice"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2205-2587","authenticated-orcid":false,"given":"Eliana","family":"Rosa Lima","sequence":"first","affiliation":[{"name":"Biotechnology Center, Instituto de Pesquisas Energ\u00e9ticas e Nucleares (IPEN-CNEN), Cidade Universit\u00e1ria, 05508-000 S\u00e3o Paulo, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Regina Cecchi","sequence":"additional","affiliation":[{"name":"Biotechnology Center, Instituto de Pesquisas Energ\u00e9ticas e Nucleares (IPEN-CNEN), Cidade Universit\u00e1ria, 05508-000 S\u00e3o Paulo, SP, Brazil"},{"name":"Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eliza","family":"Higuti","sequence":"additional","affiliation":[{"name":"Biotechnology Center, Instituto de Pesquisas Energ\u00e9ticas e Nucleares (IPEN-CNEN), Cidade Universit\u00e1ria, 05508-000 S\u00e3o Paulo, SP, Brazil"},{"name":"Biotechnology Quality Control Laboratory, Butantan Institute, 05503-900 S\u00e3o Paulo, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gustavo","family":"Protasio Pacheco de Jesus","sequence":"additional","affiliation":[{"name":"Biotechnology Center, Instituto de Pesquisas Energ\u00e9ticas e Nucleares (IPEN-CNEN), Cidade Universit\u00e1ria, 05508-000 S\u00e3o Paulo, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6807-3674","authenticated-orcid":false,"given":"Alissandra","family":"Moura Gomes","sequence":"additional","affiliation":[{"name":"Biotechnology Center, Instituto de Pesquisas Energ\u00e9ticas e Nucleares (IPEN-CNEN), Cidade Universit\u00e1ria, 05508-000 S\u00e3o Paulo, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enio","family":"Aparecido Zacarias","sequence":"additional","affiliation":[{"name":"Biotechnology Center, Instituto de Pesquisas Energ\u00e9ticas e Nucleares (IPEN-CNEN), Cidade Universit\u00e1ria, 05508-000 S\u00e3o Paulo, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Bartolini","sequence":"additional","affiliation":[{"name":"Biotechnology Center, Instituto de Pesquisas Energ\u00e9ticas e Nucleares (IPEN-CNEN), Cidade Universit\u00e1ria, 05508-000 S\u00e3o Paulo, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cibele","family":"Nunes Peroni","sequence":"additional","affiliation":[{"name":"Biotechnology Center, Instituto de Pesquisas Energ\u00e9ticas e Nucleares (IPEN-CNEN), Cidade Universit\u00e1ria, 05508-000 S\u00e3o Paulo, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e3015","DOI":"10.1002\/jgm.3015","article-title":"Gene therapy trials worldwide to 2017: An update","volume":"20","author":"Ginn","year":"2018","journal-title":"J. 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