We recently developed a novel nucleic acid analogue, Bridged Nucleic Acid (BNA), one of the most promising artificial nucleic acids for antisense and/or antigene methodology. The antisense effects of BNA modified oligonucleotides targeting the Internal Ribosomal Entry Site (IRES) in Hepatitis C Virus (HCV) RNA were evaluated. As a result, it was found that the antisense BNA oligonucleotides efficiently suppressed the targeted gene-expression in a sequence specific manner. Although the stem region in the mRNA is generally thought to be out of target for the antisense strategy, BNA oligonucleotide targeting the stem region in the HCV-IRES gave a positive antisense effect, also. It is quite noteworthy.