The clinical experience of antisense therapy to ICAM-1 in Crohn's disease.
ISIS-2302 is a 6781.24 amu molecular weight antisense molecule. Its sequence is 5'-GCCCAAGCTGGCATCCGTCA-3'. This 20 base phosphorothioate hybridizes to a sequence in the 3' untranslated region of human ICAM-1 mRNA. This substrate is cleaved by RNase H, resulting in specific message and protein reduction 11,21.
Yacyshyn
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Division of Gastroenterology, University of Alberta, Edmonton, Canada. bruce.yacyshyn@ualberta.ca
Bowen-Yacyshyn
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MB
Shanahan
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D000818:Animals; D030801:Animals, Genetically Modified; D001327:Autoimmune Diseases / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D003092:Colitis / Q000188:drug therapy; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D004311:Double-Blind Method; D004353:Drug Evaluation, Preclinical; D015316:Genetic Therapy; D015796:HLA-B27 Antigen / Q000235:genetics; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000235:genetics*; D051379:Mice; D023421:Models, Animal; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D020319:Oligodeoxyribonucleotides, Antisense / Q000737:chemistry / Q000627:therapeutic use*; D020320:Oligoribonucleotides, Antisense / Q000627:therapeutic use; D054735:Phosphorothioate Oligonucleotides; D010865:Pilot Projects; D012333:RNA, Messenger / Q000037:antagonists & inhibitors*; D051381:Rats; D012074:Remission Induction; D012449:Safety; D013873:Thionucleotides / Q000737:chemistry / Q000627:therapeutic use*; D016896:Treatment Outcome; D001613:beta 2-Microglobulin / Q000235:genetics
D015796:HLA-B27 Antigen; C442330:ISIS 9125; D016328:NF-kappa B; D020319:Oligodeoxyribonucleotides, Antisense; D020320:Oligoribonucleotides, Antisense; D054735:Phosphorothioate Oligonucleotides; D012333:RNA, Messenger; D013873:Thionucleotides; D001613:beta 2-Microglobulin; D018799:Intercellular Adhesion Molecule-1; C089753:alicaforsen