tetracycline and arginyl-glycyl-aspartic-acid

Previously, we developed single adenovirus (Ad) vectors that contained the gene of interest in the E1 deletion region and the transactivator gene for the tetracycline-controllable expression system in the E3 deletion region. In the present study, we improved the Ad vector-mediated tetracycline-controllable expression system by the fiber modification of Ad. We developed fiber-modified Ad vectors containing the tet-off system, which are effective in overcoming the limitations of conventional Ad vectors, specifically their inefficient gene transfer into cells lacking the primary receptor, the coxsackievirus and adenovirus receptor (CAR). Ad vectors containing the tet-off system with an Arg-Gly-Asp (RGD) peptide in the HI loop of the fiber knob or the Ad type 35 fiber greatly improved transduction efficiency (more than 1-2-log orders) into the cells lacking CAR expression but expressing alphav integrin or CD46, respectively. They exhibited vastly higher regulation of gene expression by doxycycline. The combination of fiber-modified Ad vectors and the tetracycline-controllable expression system should offer a powerful tool for gene therapy and gene transfer experiment.

Topics: Adenoviridae; Animals; Capsid Proteins; Cell Line, Tumor; CHO Cells; Coxsackie and Adenovirus Receptor-Like Membrane Protein; Cricetinae; Doxycycline; Gene Expression Regulation; Genetic Vectors; Humans; Integrin alphaV; Membrane Cofactor Protein; Mice; NIH 3T3 Cells; Oligopeptides; Receptors, Virus; Tetracycline; Transduction, Genetic; Transfection

To investigate the distribution of tetracycline-arginine-glycine-aspartate-tyrosine (T-RGDY) in mice and its effect on bone.. 125-labeled T-RGDY was studied for its distribution in mice and for its effects on bone by histomorphometry in ovariectomized rats.. The 125I-labeled T-RGDY was more concentrated in the osteoporotic bone than in the normal bone. Compared with ovariectomy group, the morphologic index such as trabecular bone volume/total tissue volume (TBV/TTV), TBV/sponge bone volume (SBV), and mean trabecular plate thickness (MTPT) in T-RGDY group significantly increased (P < 0.05). As compared with sham operation group, MTPT significantly increased in T-RGDY group (P < 0.05), while TBV/SBV and mean trabecular plate density significantly decreased (P < 0.05), and TBV/TYV and mean trabecular plate spacing were almost the same as those in sham operation group (P > 0.05).. T-RGDY may concentrate in bone tissue to a certain degree, which is closely related with the status of bone remodeling. T-RGDY may inhibit the bone loss caused by ovariectomy.

Topics: Animals; Bone Density; Bone Remodeling; Female; Mice; Oligopeptides; Osteoporosis; Ovariectomy; Rats; Rats, Sprague-Dawley; Tetracycline; Tissue Distribution; Tyrosine