Growth Responses Following a Single Intra-Muscular hGH Plasmid Administration Compared to Daily Injections of hGH in Dwarf Mice

dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorHIGUTI, Eliza
dc.contributor.authorCECCHI, Claudia R.
dc.contributor.authorOLIVEIRA, Nelio A. J.
dc.contributor.authorVIEIRA, Daniel P.
dc.contributor.authorJENSEN, Thomas G.
dc.contributor.authorJORGE, Alexander A. L.
dc.contributor.authorBARTOLINI, Paolo
dc.contributor.authorPERONI, Cibele N.
dc.date.accessioned2013-07-30T14:41:59Z
dc.date.available2013-07-30T14:41:59Z
dc.date.issued2012
dc.description.abstractIn previous work, sustained levels of circulating human growth hormone (hGH) and a highly significant weight increase were observed after electrotransfer of naked plasmid DNA (hGH-DNA) into the muscle of immunodeficient dwarf mice (lit/scid). In the present study, the efficacy of this in vivo gene therapy strategy is compared to daily injections (5 mu g/twice a day) of recombinant hGH (r-hGH) protein, as assessed on the basis of several growth parameters. The slopes of the two growth curves were found to be similar (P>0.05): 0.095 g/mouse/d for protein and 0.094 g/mouse/d for DNA injection. In contrast, the weight increases averaged 35.5% (P<0.001) and 23.1% (P<0.01) for protein and DNA administration, respectively, a difference possibly related to the electroporation methodology. The nose-to-tail linear growth increases were 15% and 9.6% for the protein and DNA treatments, respectively, but mouse insulin-like growth factor I (mIGF-I) showed a greater increase over the control with DNA (5- to 7-fold) than with protein (3- to 4-fold) administration. The weight increases of several organs and tissues (kidneys, spleen, liver, heart, quadriceps and gastrocnemius muscles) were 1.3- to 4.6-fold greater for protein than for DNA administration, which gave a generally more proportional growth. Glucose levels were apparently unaffected, suggesting the absence of effects on glucose tolerance. A gene transfer strategy based on a single hGH-DNA administration thus appears to be comparable to repeated hormone injections for promoting growth and may represent a feasible alternative for the treatment of growth hormone deficiency.
dc.description.indexMEDLINE
dc.description.sponsorshipFAPESP, Sao Paulo, Brazil [2010/51116-0, 2010/51848-1, 2011/21708-6]
dc.description.sponsorshipNational Research Council (CNPq), Brasilia, Brazil [143639/2008-0, PQ 300473/2009-5]
dc.identifier.citationCURRENT GENE THERAPY, v.12, n.6, p.437-443, 2012
dc.identifier.doi10.2174/156652312803519797
dc.identifier.issn1566-5232
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/514
dc.language.isoeng
dc.publisherBENTHAM SCIENCE PUBL LTD
dc.relation.ispartofCurrent Gene Therapy
dc.rightsrestrictedAccess
dc.rights.holderCopyright BENTHAM SCIENCE PUBL LTD
dc.subjecthuman growth hormone
dc.subjectimmunodeficient little mice
dc.subjectmouse insulin-like growth factor I
dc.subjectnaked DNA
dc.subject.otherhormone-releasing-hormone
dc.subject.otherphase-i trial
dc.subject.otherprimary human keratinocytes
dc.subject.otherlong-term growth
dc.subject.othergene-therapy
dc.subject.otherhypophysectomized mice
dc.subject.otheranimal-model
dc.subject.otherexpression
dc.subject.otherelectroporation
dc.subject.otherdeficiency
dc.subject.wosGenetics & Heredity
dc.titleGrowth Responses Following a Single Intra-Muscular hGH Plasmid Administration Compared to Daily Injections of hGH in Dwarf Mice
dc.typearticle
dc.type.categoryreview
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.affiliation.countryDinamarca
hcfmusp.affiliation.countryisodk
hcfmusp.author.externalHIGUTI, Eliza:Natl Nucl Energy Commiss IPEN CNEN, Dept Biotechnol, Sao Paulo, Brazil
hcfmusp.author.externalCECCHI, Claudia R.:Natl Nucl Energy Commiss IPEN CNEN, Dept Biotechnol, Sao Paulo, Brazil
hcfmusp.author.externalOLIVEIRA, Nelio A. J.:Natl Nucl Energy Commiss IPEN CNEN, Dept Biotechnol, Sao Paulo, Brazil
hcfmusp.author.externalVIEIRA, Daniel P.:Natl Nucl Energy Commiss IPEN CNEN, Dept Biotechnol, Sao Paulo, Brazil
hcfmusp.author.externalJENSEN, Thomas G.:Aarhus Univ, Dept Biomed, DK-8000 Aarhus C, Denmark
hcfmusp.author.externalBARTOLINI, Paolo:Natl Nucl Energy Commiss IPEN CNEN, Dept Biotechnol, Sao Paulo, Brazil
hcfmusp.author.externalPERONI, Cibele N.:Natl Nucl Energy Commiss IPEN CNEN, Dept Biotechnol, Sao Paulo, Brazil
hcfmusp.citation.scopus5
hcfmusp.contributor.author-fmusphcALEXANDER AUGUSTO DE LIMA JORGE
hcfmusp.description.beginpage437
hcfmusp.description.endpage443
hcfmusp.description.issue6
hcfmusp.description.volume2012
hcfmusp.lim.ref2012
hcfmusp.origemWOS
hcfmusp.origem.pubmed22974419
hcfmusp.origem.scopus2-s2.0-84870164679
hcfmusp.origem.wosWOS:000313577900001
hcfmusp.publisher.citySHARJAH
hcfmusp.publisher.countryU ARAB EMIRATES
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hcfmusp.remissive.sponsorshipCNPq
hcfmusp.remissive.sponsorshipFAPESP
hcfmusp.scopus.lastupdate2024-05-17
relation.isAuthorOfPublication872493f0-3232-484e-a574-207e16fcf202
relation.isAuthorOfPublication.latestForDiscovery872493f0-3232-484e-a574-207e16fcf202
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