Targeting the expression of anti-apoptotic proteins by antisense oligonucleotides.
Antisense oligonucleotide (ASO) biotechnology has been widely used to inhibit the expression of proteins involved in human disease. ASOs are designed to bind messenger RNA transcripts via Watson-Crick base-pairing and inhibit synthesis of targeted proteins. These proteins include protein kinases, growth factors, glutamate receptors, anti-apoptotic proteins, and proteins involved in genetic disorders. Non-mRNA targets such as the RNA component of the telomerase enzyme are also being explored. Pre-clinical and clinical trials using ASO biotechnology have progressed with standard ASOs such as phosphorothioates, but newer ASO analogs are rapidly being developed with the idea of enhancing specificity and biological activity. A current major research thrust is the design and testing of antisense oligonucleotides as anti-cancer drugs. The primary focus of this review is an analysis of recent uses of ASO biotechnology to inhibit anti-apoptotic gene expression in tumor cells.
Delihas
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Department of Molecular Genetics and Microbiology, School of Medicine, SUNY, Stony Brook, NY 11794-5222, USA. nicholas.delihas@sunysb.edu
D002986:Clinical Trials as Topic; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D015195:Drug Design; D006801:Humans; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000235:genetics; D051818:Replication Protein C; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D004268:DNA-Binding Proteins; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D051818:Replication Protein C