感应(电子)
化学
小干扰RNA
核糖核酸
核苷
感觉链
赫拉
RNA干扰
反义RNA
立体化学
核苷酸
生物化学
分子生物学
体外
生物
基因
物理化学
作者
Thazha P. Prakash,Charles R. Allerson,Prasad Dande,Timothy A. Vickers,Namir Sioufi,Russell Jarres,Brenda F. Baker,Eric E. Swayze,Richard H. Griffey,Balkrishen Bhat
摘要
A systematic study on the effect of 2'-sugar modifications (2'-F (2'-F-2'-deoxy-nucleoside residues), 2'-O-Me (2'-O-methyl-nucleoside residues), and 2'-O-MOE [2'-O-(2-methoxyethyl)]-nucleoside residues) in the antisense and sense strands of short interference RNA (siRNA) was performed in HeLa cells. The study of the antisense strand of siRNAs demonstrated that activity depends on the position of the modifications in the sequence. The siRNAs with modified ribonucleotides at the 5'-end of the antisense strand were less active relative to the 3'-modified ones. The 2'-F sugar was generally well-tolerated on the antisense strand, whereas the 2'-O-Me showed significant shift in activity depending on the position of modification. The 2'-O-MOE modification in the antisense strand resulted in less active siRNA constructs regardless of placement position in the construct. The incorporation of the modified residues, e.g., 2'-O-Me and 2'-O-MOE, in the sense strand of siRNA did not show a strong positional preference. These results may provide guidelines to design effective and stable siRNAs for RNA interference mediated therapeutic applications.
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