Draghia-Akli Ruxandra, Malone P Brandon, Hill Leigh Anne, Ellis Kenneth M, Schwartz Robert J, Nordstrom Jeffrey L
Department of Molecular and Cellular Biology, Center for Cell and Gene Therapy, ASR-USDA Baylor College of Medicine, Houston, Texas 77030, USA.
FASEB J. 2002 Mar;16(3):426-8. doi: 10.1096/fj.01-0702fje. Epub 2002 Jan 14.
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ligand mifepristone (MFP) up-regulated GHRH expression, as shown by elevations of IGF-I levels, and when MFP dosing was withdrawn, IGF-I returned to baseline levels.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.
在成年SCID小鼠的胫前肌中单次电穿孔注射两种质粒（10微克DNA）的混合物后，出现了受调控的动物生长。这两种质粒，一种表达基因开关调节蛋白，另一种是可诱导的生长激素释放激素（GHRH）基因。给予配体米非司酮（MFP）上调了GHRH的表达，这通过IGF-I水平的升高得以体现，并且当停止给予MFP时，IGF-I恢复到基线水平。在五个月的时间里观察到了五个周期的IGF-I诱导。与未用MFP处理的对照组相比，连续25天给予慢性MFP显著增加了瘦体重、体重增加和骨矿物质密度。总之，基于质粒的基因治疗后实现了长期药物调控的GHRH表达，并且成年动物中GHRH表达的慢性诱导导致体重增加和身体组成的改善。
