PMID- 22974419 OWN - NLM STAT- MEDLINE DCOM- 20130528 LR - 20191112 IS - 1875-5631 (Electronic) IS - 1566-5232 (Linking) VI - 12 IP - 6 DP - 2012 Dec TI - Growth responses following a single intra-muscular hGH plasmid administration compared to daily injections of hGH in dwarf mice. PG - 437-43 AB - In 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 mug/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. FAU - Higuti, Eliza AU - Higuti E AD - Biotechnology Department, National Nuclear Energy Commission (IPEN-CNEN), Cidade Universitaria, Sao Paulo, SP, Brazil. FAU - Cecchi, Claudia R AU - Cecchi CR FAU - Oliveira, Nelio A J AU - Oliveira NA FAU - Vieira, Daniel P AU - Vieira DP FAU - Jensen, Thomas G AU - Jensen TG FAU - Jorge, Alexander A L AU - Jorge AA FAU - Bartolini, Paolo AU - Bartolini P FAU - Peroni, Cibele N AU - Peroni CN LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United Arab Emirates TA - Curr Gene Ther JT - Current gene therapy JID - 101125446 RN - 0 (Blood Glucose) RN - 0 (Recombinant Proteins) RN - 12629-01-5 (Human Growth Hormone) RN - 67763-96-6 (Insulin-Like Growth Factor I) SB - IM MH - Animals MH - Blood Glucose/analysis MH - Dwarfism/drug therapy/metabolism MH - Electroporation MH - Gene Transfer Techniques MH - Genetic Therapy/*methods MH - Heart/drug effects/*growth & development MH - Human Growth Hormone/administration & dosage/genetics/*pharmacology MH - Humans MH - Injections, Intramuscular MH - Insulin-Like Growth Factor I/metabolism MH - Kidney/drug effects/*growth & development MH - Liver/drug effects/*growth & development MH - Mice MH - Mice, Inbred BALB C MH - Mice, SCID MH - Organ Size MH - Plasmids/*administration & dosage MH - Recombinant Proteins/administration & dosage/pharmacology MH - Spleen/drug effects/growth & development MH - Time Factors MH - Weight Gain EDAT- 2012/09/15 06:00 MHDA- 2013/05/29 06:00 CRDT- 2012/09/15 06:00 PHST- 2012/03/21 00:00 [received] PHST- 2012/07/04 00:00 [revised] PHST- 2012/07/06 00:00 [accepted] PHST- 2012/09/15 06:00 [entrez] PHST- 2012/09/15 06:00 [pubmed] PHST- 2013/05/29 06:00 [medline] AID - CGT-EPUB-20120911-2 [pii] AID - 10.2174/156652312803519797 [doi] PST - ppublish SO - Curr Gene Ther. 2012 Dec;12(6):437-43. doi: 10.2174/156652312803519797.