Sequence-specific photo-induced c-fos gene damage mediated by triple stranded-forming oligonucleotide conjugated to psoralen

摘要

A psoralen- oligonucleotide conjugate was designed to photoinduce a cross-link at a specific sequence of c-fos oncogene. Psoralen was attached to its C-3 position of a 20-base mer oligonucleotide, which binds to a synthetic 49 bp duplex containing the c-fos gene polypurine site, where it forms a triple stranded DNA. Upon near-UV-irradiation, the two strand of DNA are crosslinked at the TpA step present at the triple-duplex junction. Results show that the yield of the photoinduce cross-linking reaction is quite high. We treated HeLa cells with above 20-mer oligonucleotide conjugated to psoralen. The expression of c-fos oncogene was significantly reduced, no significant effect on the level of c-myc mRNA. These data indicate that such psoralen-oligonucleotide conjugates could be used to selectively control gene expression or to induce Sequence-specific damages.