Nucleic acid drugs for prevention of cardiac rejection.
Heart transplantation has been broadly performed in humans. However, occurrence of acute and chronic rejection has not yet been resolved. Several inflammatory factors, such as cytokines and adhesion molecules, enhance the rejection. The graft arterial disease (GAD), which is a type of chronic rejection, is characterized by intimal thickening comprised of proliferative smooth muscle cells. Specific treatments that target the attenuation of acute rejection and GAD formation have not been well studied in cardiac transplantation. Recent progress in the nucleic acid drugs, such as antisense oligodeoxynucleotides (ODNs) to regulate the transcription of disease-related genes, has important roles in therapeutic applications. Transfection of cis-element double-stranded DNA, named as "decoy," has been also reported to be a useful nucleic acid drug. This decoy strategy has been not only a useful method for the experimental studies of gene regulation but also a novel clinical strategy. In this paper, we reviewed the experimental results of NF-kappaB, E2F, AP-1, and STAT-1 decoy and other ODNs using the experimental heart transplant models.
Suzuki
Jun-ichi
J
Department of Advanced Clinical Science and Therapeutics, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan. junichisuzuki-circ@umin.ac.jp
Isobe
Mitsuaki
M
Morishita
Ryuichi
R
Nagai
Ryozo
R
D000818:Animals; D006084:Graft Rejection / Q000188:drug therapy* / Q000517:prevention & control*; D016027:Heart Transplantation; D006801:Humans; D009696:Nucleic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D009838:Oligodeoxyribonucleotides / Q000627:therapeutic use; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use
D009696:Nucleic Acids; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense