Monitoring of antisense effects of oligonucleotides targeted to the neuropeptide Y Y-1 receptor gene

The suppression of neuropeptide Y Y-1 receptor gene expression by antisense oligonucleotides targeted to different gene regions was monitored on mRNA and protein level in the human neuroblastoma SK-N-MC cell line. The antisense oligonucleotide targeted to the junction of the first intron and second exon suppressed specifically Y-1 receptor subtype number by more than 50%, but only if oligonucleotides were administered by electroporation. Also, the formation of Y-1 receptor mRNA as shown by reverse transcription-polymerase chain reaction was markedly blocked in this case. Using the antisense oligonucleotide targeted to the start of translation, no effect, neither on the Y-1, receptor number nor on Y-1 receptor mRNA, could be observed. This finding suggests that besides sequence-specific effects of antisense oligonucleotides gene site-specific effects play a major role in the efficacy of suppression. (C) 1997 Elsevier Science B.V.