Systemic effect of human growth hormone after intramuscular injection of a single dose of a muscle-specific gene medicine

被引：47

作者：

Anwer, K ^{[1
]}

Shi, M ^{[1
]}

French, MF ^{[1
]}

Muller, SR ^{[1
]}

Chen, W ^{[1
]}

Liu, QS ^{[1
]}

Proctor, BL ^{[1
]}

Wang, JJ ^{[1
]}

Mumper, RJ ^{[1
]}

Singhal, A ^{[1
]}

Rolland, AP ^{[1
]}

Alila, HW ^{[1
]}

机构：

[1] GeneMed Inc, The Woodlands, TX 77381 USA

来源：

HUMAN GENE THERAPY | 1998年 / 9卷 / 05期

关键词：

D O I：

10.1089/hum.1998.9.5-659

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 [微生物学]; 0836 [生物工程]; 090102 [作物遗传育种]; 100705 [微生物与生化药学];

摘要：

A muscle-specific gene medicine is described that provides for long-term secretion of biologically active human growth hormone (hGH) from skeletal muscle into the systemic circulation. The hGH gene medicine is composed of a muscle-specific hGH plasmid expression system complexed with a protective, interactive, noncondensing (PINC(TM)) delivery system. The muscle-specific gene expression system, pSK-hGH-GH, was constructed by linking the promoter/enhancer regions of chicken skeletal alpha-actin to hGH gene. C2C12 myoblast transfection with pSK-hGH-GH resulted in the synthesis of hGH in a muscle-specific manner. Direct injection into rat tibialis cranialis muscle of pSK-hGH-GH complexed with a polymeric PINC delivery system, polyvinylpyrrolidone (PVP), produced hGH levels in muscle that were 10- to 15-fold higher compared with plasmid formulated in saline at 14 days post-injection. Intratracheal instillation in rat lung of pSK-hGH-GH did not produce significantly detectable levels of hGH. In hypophysectomized rats, a single intramuscular dose of the pSK-hGH-GH/PVP complex resulted in hGH expression and a subsequent increase in serum levels of rat ICE-I and growth. hCH expression and effects on rat serum ICE-I levels were detectable up to 28 days after injection of formulated plasmid and effects on growth were detectable unto 21 days. Anti-hGH antibodies were detectable in serum at 14 days post-injection, reached a plateau at 21 days, and remained elevated through the study period. Cyclosporin treatment of the pSK-hGH-GH/PVP-injected animals completely inhibited the antibody response and resulted in increased hGH expression.

引用

页码：659 / 670

页数：12

共 37 条

[1]

Expression of biologically active human insulin-like growth factor-I following intramuscular injection of a formulated plasmid in rats [J].