Bovine epithelial cells originally transfected with lipofectin-negative mutant demonstrated significantly reduced luciferase activity, although the efficiency of transfection was low. A replication deficient adenovirus construct demonstrated increased transfection efficiency as well as greater inhibition of signal transduction as measured by decreased 3H thymidine incorporation into porcine smooth muscle cells. The adenovirus vector control indicated the vector itself did not effect cellular mitosis. Researchers at UCSD have discovered that the upstream signal transduction pathways leading to the activation of the cis-elements are mediated through several cellular proteins. The feature of this invention is that, by transfecting the mutants of these proteins, the researchers were able to block the gene expression in the vascular cells induced by hemodynamic forces as well as cytokines.
Hemodynamic forces play a key role in the onset of restinosis.
Several cis-regulatory elements present in the promoter regions of restinosis related genes respond to these forces and are responsible for expression of those genes after cardiac repair procedures. This invention uses negative mutants of genes which regulate a signal transduction pathway upstream from the regulatory elements. The constructs block the expression of these restinosis related genes. This invention will enable a therapeutic procedure in parallel with balloon angioplasty and coronary bypass to reduce the occurrence of restinosis.