Solid-phase synthesis of modified RNAs containing amide-linked oligoribonucleosides at their 3'-end and their application to siRNA.
siRNAs against luciferase mRNA were modified with amide-linked oligoribonucleosides (amide-linked RNA) at their 3 '-overhangs. Tm values of the modified siRNAs increased compared with that of the unmodified siRNA. These results indicate that the modified overhangs increase the thermodynamic stability of the siRNAs. The modified overhangs improved stability of siRNAs against degradation by nuclease S1 and 50% mouse plasma. Furthermore the modified siRNAs reduced the target gene expression in a similar manner to the unmodified siRNA in cultured cells. These results suggest that the overhang modifications are tolerated for the siRNA activity.
Iwase
Reiko
R
Department of Biosciences, Teikyo University of Science and Technology, 2525 Yatsusawa, Uenohara, Yamanashi 409-0193, Japan. iwase@ntu.ac.jp
Toyama
Takaaki
T
Nishimori
Kengo
K
D000577:Amides / Q000737:chemistry*; D000818:Animals; D001483:Base Sequence; D049410:Luciferases, Renilla / Q000037:antagonists & inhibitors / Q000235:genetics; D009843:Oligoribonucleotides / Q000737:chemistry*; D012313:RNA / Q000138:chemical synthesis* / Q000737:chemistry; D020871:RNA Stability; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000494:pharmacology
D000577:Amides; D009843:Oligoribonucleotides; D034741:RNA, Small Interfering; D012313:RNA; D049410:Luciferases, Renilla