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-α subunit of protein kinase A, a gene whose expression has been associated with many types of cancer [273331,275860].