Technology evaluation: GEM-231, Hybridon Inc.
Hybridon is conducting studies of the DNA methyltransferase gene and has identified specific sequences on mRNA as targets for chemically-modified antisense oligonucleotides. Hybridon has synthesized compounds that alter methylation of cultured human cancer cells and inhibit their ability to grow in cell culture and inhibit tumor formation in mice [191303]. The work is being carried out in collaboration with McGill University in Montreal and as part of a joint venture called MethylGene, set up by Hybridon and private investors. GEM-231 (a mixed backbone oligonucleotide) is a strand of synthetic DNA, which has been modified with 2'-O-methyl ribose at both ends in order to resemble RNA. It has the ability to inhibit expression of the R1-alpha subunit of protein kinase A, a gene whose expression has been associated with many types of cancer [273331,275860].
Department of Pharmacology, Faculty of Medicine, Sir Charles Tupper Building, Dalhousie University, Halifax, Nova Scotia, B3H 4H7, Canada. jblay@is.dal.ca
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D000818:Animals; D001709:Biotechnology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D016376:Oligonucleotides, Antisense / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D016376:Oligonucleotides, Antisense; D017868:Cyclic AMP-Dependent Protein Kinases