Loss of silencing activity caused by 5′-terminal modification with d-/l-isonucleotide (isoNA) or locked nucleic acid (LNA) could not be restored by 5′-terminal phosphorylation

• DOI: 10.1007/s11426-013-5032-4
• Publication Date: 2013-12-19T04:56:48Z
• Authors: Ye Huang; Zhuo Chen; Zhuo Wang; YaTing Li; Yue Chen; ZhenJun Yang; LiHe Zhang
• Keywords: 0301 basic medicine; 03 medical and health sciences

In this study, a series of 5′-phosphorylated siRNAs with d-/l-isonucleotide (isoNA) or locked nucleic acid (LNA) incorporated at the 5′-terminus were synthesized. It was found that after incorporating either isoNA or LNA at the 5′-terminus of the antisense strand or sense strand, the silencing activity of modified strands has been inhibited, which cannot be recovered by phosphorylation at the 5′-terminus; however, the silencing activity of unmodified strand to its own target was increased. This work indicates that the isoNA and LNA modification at 5′-terminus can interfere with the strand selection during the RISC assembling process, and the disturbance of the 5′-phosporylation should not be the only viable mechanism.