IN-VIVO TRANSFECTION OF CIS-ELEMENT DECOY AGAINST NUCLEAR FACTOR-KAPPA-B BINDING-SITE PREVENTS MYOCARDIAL-INFARCTION

The transcriptional factor nuclear factor-kappa B (NF kappa B) plays a pivotal role in the coordinated transactivation of cytokine and adhes ion molecule genes that might be Involved in myocardial damage after i schemia and reperfusion. Therefore, we hypothesized that synthetic dou ble-stranded DNA with high affinity for NF kappa B could be introduced in vivo as ''decoy'' cls elements to bind the transcriptional factor and to block the activation of genes mediating myocardial infarction, thus providing effective therapy for myocardial infarction. Treatment before and after infarction by transfection of NF kappa B decoy, but n ot scrambled decoy, oligodeoxynucleotides before coronary artery occlu sion or immediately after reperfusion had a significant inhibitory eff ect on the area of infarction. Here, we report the first successful in vivo transfer of NF kappa B decoy oligodeoxynucleotides to reduce the extent of myocardial infarction following reperfusion, providing a ne w therapeutic strategy for myocardial infarction.