Enhanced animal growth via ligand-regulated GHRH myogenic-injectable vectors.
Regulated animal growth occurred following a single electroporated injection of a mixture of two plasmids (10 microg of DNA), one expressing the GeneSwitch regulator protein, the other an inducible growth hormone releasing hormone (GHRH) gene, into the tibialis anterior muscles of adult SCID mice. Administration of the ligand mifepristone (MFP) up-regulated GHRH expression, as shown by elevations of IGF-I levels, and when MFP dosing was withdrawn, IGF-I returned to baseline levels. Five cycles of IGF-I induction were observed during a five-month period. Chronic MFP dosing for 25 days increased lean body mass, weight gain, and bone mineral density significantly compared with non-MFP treated controls. In summary, long-term drug-regulated GHRH expression was achieved following plasmid-based gene therapy, and chronic induction of GHRH expression in adult animals led to improvements in weight gain and body composition.
Draghia-Akli
Ruxandra
R
Department of Molecular and Cellular Biology, Center for Cell and Gene Therapy, ASR-USDA Baylor College of Medicine, Houston, Texas 77030, USA. ada@bcm.tmc.edu
Malone
P Brandon
PB
Hill
Leigh Anne
LA
Ellis
Kenneth M
KM
Schwartz
Robert J
RJ
Nordstrom
Jeffrey L
JL
D000818:Animals; D001823:Body Composition; D015519:Bone Density; D002478:Cells, Cultured; D002645:Chickens; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage; D013007:Growth Hormone-Releasing Hormone / Q000235:genetics* / Q000378:metabolism; D007267:Injections; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D007700:Kinetics; D008024:Ligands; D051379:Mice; D016513:Mice, SCID; D015735:Mifepristone / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000254:growth & development / Q000378:metabolism; D010957:Plasmids; D015202:Protein Engineering / Q000379:methods; D015533:Transcriptional Activation; D015430:Weight Gain
D008024:Ligands; D015735:Mifepristone; D007334:Insulin-Like Growth Factor I; D013007:Growth Hormone-Releasing Hormone