Oligonucleotides as transcription factor decoys.
Cellular and molecular research has been focused to develop a means to regulate gene expression in an effort to treat and cure a variety of diseases and abnormal physiological conditions. A successful oligonucleotide-based approach has been the use of synthetic oligonucleotides containing an enhancer element that can penetrate cells, bind sequence-specific DNA-binding proteins and interfere with transcription in vivo. This review describes such decoy oligonucleotides that exhibit high affinity for a target transcription factor and successfully interfere with transcription in vivo. Evidence presented here shows that the decoy oligonucleotide technology offers great promise as a tool for defining cellular regulatory processes and for treating cancer, viral diseases and other pathological conditions.
Cho-Chung
Y S
YS
National Cancer Institute, Bethesda, MD 20892-1750, USA. chochung@helix.nih.gov
Park
Y G
YG
Lee
Y N
YN
D015906:Angioplasty, Balloon, Coronary; D002448:Cell Adhesion / Q000187:drug effects; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000737:chemistry; D023921:Coronary Stenosis / Q000517:prevention & control / Q000628:therapy; D000242:Cyclic AMP / Q000502:physiology; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins; D015195:Drug Design; D004355:Drug Stability; D050684:E2F Transcription Factors; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D015696:Gene Products, tat / Q000037:antagonists & inhibitors / Q000235:genetics; D015757:Genes, rev; D015756:Genes, tat; D005921:Glomerulonephritis / Q000188:drug therapy / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D009203:Myocardial Infarction / Q000188:drug therapy / Q000235:genetics; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D012008:Recurrence; D012045:Regulatory Sequences, Nucleic Acid; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D015290:Second Messenger Systems / Q000502:physiology; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology*; D014157:Transcription Factors / Q000037:antagonists & inhibitors*; D017539:Tunica Intima / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D015696:Gene Products, tat; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D018894:Reverse Transcriptase Inhibitors; D013873:Thionucleotides; D014157:Transcription Factors; D004247:DNA; D000242:Cyclic AMP; D054303:HIV Reverse Transcriptase; D013755:Tetradecanoylphorbol Acetate