Enhancers of genes

Fig. 2.2 Simplified scheme of oxidant/antioxidant regulation ofNF-KB activation. Different stimuli, leading to an increase of ROS generation inside the ceU, activate the phosphorylation of IkB inhibitory protein and the subsequent proteolysis. Thioredoxin (Trx) may reduce activated NF-kB proteins facilitating nuclear translocation.Qnce released from IkB, the NF-kB complex translocates into the nucleus and the binding to DNA domain in the promoters and enhancers of genes such as TNF-a, IL-1, proliferation and chemotactic factors, adhesion molecule. Some of these genes, in turn, may further induce NF-kB activation, leading to a vicious circle if the regulatory cellular system escapes from...

Arima, H., F. Kihara, F. Hirayama, and K. Uekama. 2001. Enhancement of gene expression by polyamidoamine dendrimer conjugates with alpha-, beta-, and gamma-cyclodextrins. Bioconjug Chem 12(4) 476-84. 

Shibata, T., Akiyama, N., Noda, M., Sasai, K. and Hiraoka, M. (1998) Enhancement of gene expression under hypoxic conditions using fragments of the human vascular endothelial growth factor and the erythropoietin genes. Int.J. Radiat. Oncol. Biol. Rhys., 42, 913-916. 

Li, S., MacLaughlin, F.C., Fewell, J.G., Gondo, M., Wang, J., Nicol, F. et al. (2001) Muscle-specific enhancement of gene expression by incorporation of the SV40 enhancer in the expression plasmid. Gene Ther., 8, 494 197. 

Schambach, A., Wodrich, H., Hildinger, M., Bohne, J., Krausslich, H.G. and Baum, C. (2000) Context dependence of different modules for posttranscriptional enhancement of gene expression from retroviral vectors. Mol. Ther., 2, 435 145. 

Rebuffat A, Bemasconi A, Ceppi M, Wehrli H, Verca SB, Ibrahim M, Frey BM, Frey FJ, Rusconi S. Selective enhancement of gene transfer by steroid-mediated gene delivery. Nat Biotechnol 2001, 19, 1155-1161. 

Arima, H., Kihara, F., Hirayama, F. and Uekama, K. (2001) Enhancement of gene expression by polyamidoamine dendrimer conjugates with a-, P-, and y-cyclodextrin. Bioconjugate. Chem. 12 476-484 Kihara, F., Arima, H., Tsutsumi, T. et al. (2002) Effects of structure of polyamidoamine dendrimer of gene transfer efficiency of the dendrimer conjugate with a-cyclodextrin. ibid. 13 1211-1219. 

Current strategies to improve productivity and secretion efficiency comprise (1) enhancement of gene expression rates, (2) optimization of secretion signal sequences, (3) coexpression of chaperones and foldases, (4) creation of protease deficient mutants to avoid premature product degradation, and (5) subsequent breeding and mutagenesis. 

Enhancement of gene expression in muscle Potent prodrug substance... 

Generally, polymers modified with histidine or other moieties containing an imidazole group have shown significant enhancement of gene expression without... 

Unexpectedly, the PPE-EA/DNA complexes with N/P ratios of 1.5 and 2 were ineffective. It is likely that the slow release of plasmid DNA in the muscle due to the degradation of PPE-EA resulted in this enhancement of gene expression. 

Once the complexes are taken up into endocytic vesicles, they are largely retained in the endosomes or lysosomes and are either degraded or inactivated. Therefore, the ability of the complexes to avoid these fates is an important requirement for enhancement of gene transfer upon internalization. One approach for enhancement of the release of the gene from the endosome involves use of a vector with a high buffering capacity and the flexibility to swell when protonated [30]. Among non-viral vectors, PEI reduces acidification of the endosome, induces an extensive inflow of ions and water, and subsequently leads to rupture of the endosomal membrane [7]. 

---