| 摘要 |
The promoter of the EPCR gene has been isolated from both murine (SEQ. ID No. 1) and human (SEQ. ID No. 2) genomic libraries. The promoter includes a region (nucleotides 3130 to 3350 of SEQ. ID No. 1 which affects selective gene expression in endothelial cells), and a region (nucleotides 2270 to 2840 of SEQ. ID No. 1) which affects selective gene expression in large vessel endothelial cells, as compared to expression in all endothelial cells. The EPCR promoter contains a thrombin responsive element, CCCACCCC (SEQ. ID No. 3), (murine, nucleotides 3007 to 3014 SEQ. ID No. 1 and human, nucleotides 2722 to 2729 SEQ. ID No. 2). The EPCR also contains a serum response element (nucleotides 2990 to 3061 of SEQ. ID No. 1). The regulatory sequences present in the EPCR promoter can be used for thrombin or serum controlled recombinant gene expression specific to either all endothelial cells or primarily endothelial cells of large vessels. Therapeutic strategies include the use of the minimal promoter for expression of therapeutic agents during times of increased thrombin/platelet activation or regional trauma in all endothelial cells or the use of the large vessel specific promoter for regional specific expression in the endothelial cells of large vessels for use in delivery. |
