Targeted cross-linking of the human beta-globin gene in living cells mediated by a triple helix forming oligonucleotide

The synthesis of triple helix forming oligonucleotide (TFOs) designed to target a site in the human beta-globin gene, which is the locus for mutations that underlie the beta-globinpathies, including sickle cell anemia is described. The results validate the modification format described and indicate that 2'-O-methylpseudoisocytidine substitutions are an effective solution to problem of targeting genomic sequences containing adjacent cystosines.