Edifoligide: a transcription factor decoy to modulate smooth muscle cell proliferation in vein bypass.
The era of genomics and recombinant DNA technology has ushered in an entirely new class of therapeutic agents designed to influence disease progression at a genetic level. The scope and utility of this technology is not fully realized. However, multiple trials of therapeutic agents have been completed and many more are ongoing. Here we report on edifoligide, a double-stranded oligodeoxynucleotide (ODN) that competitively inhibits the transcription factor E2F, a critical regulator of the cell cycle. Edifoligide has undergone extensive clinical testing for the treatment of intimal hyperplasia following vascular bypass procedures. In this review we address the rationale for targeting E2F in vascular disease, the pharmacology of edifoligide, and the results of preclinical and clinical studies using this novel compound.
Hoel
Andrew W
AW
Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital, Boston, MA 02115, USA.
Conte
Michael S
MS
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D001026:Coronary Artery Bypass; D050684:E2F Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics; D006083:Graft Occlusion, Vascular / Q000517:prevention & control*; D006801:Humans; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D009841:Oligonucleotides / Q000235:genetics / Q000494:pharmacology*
D050684:E2F Transcription Factors; D009841:Oligonucleotides; C502518:edifoligide