RNA interference by 2′,5′-linked nucleic acid duplexes in mammalian cells

Synthetic small interfering RNA (siRNA) mediated silencing of a specific gene is emerging as a powerful tool for gene regulation. However, their utility is limited for therapeutic applications primarily due to poor stability. The 2′,5′-linked oligonucleotides are known to be more stable to nucleolytic degradation than 3′,5′-linked oligonucleotides. The 2′,5′-linkage is tolerated in the sense strand of the siRNA duplex. However, the 2′,5′-linkage is not tolerated in the antisense strand of the siRNA duplex.