Issue 24, 2017

Isonucleotide incorporation into middle and terminal siRNA duplexes exhibits high gene silencing efficacy and nuclease resistance

Abstract

In this study, we introduced a pair of nucleotide enantiomers, D-/L-isonucleotides (D-/L-isoNA), to examine the interactions between siRNAs and their related proteins. The serum stability and gene-silencing activity of the modified siRNAs were systematically evaluated. Gene-silencing activity had a site-specific effect, and the incorporation of a single D-isoNA at the 8th position (counting from the 5′-terminus) in the antisense strand improved the gene-silencing activity by improving RISC loading and affecting the movement of the PIWI domain. D-isoNA incorporated at the terminus of siRNA including the 2nd position in the antisense strand and 3′-overhangs in the sense strand, especially the latter, enhanced nuclease resistance and prolonged the silencing retention time. In addition, L-isoNA incorporation into the middle of the sense strand enhanced activity. These results provide a chemical strategy for the modulation of siRNA gene-silencing activity and nuclease resistance.

Graphical abstract: Isonucleotide incorporation into middle and terminal siRNA duplexes exhibits high gene silencing efficacy and nuclease resistance

Supplementary files

Article information

Article type
Paper
Submitted
02 Mai 2017
Accepted
25 Mai 2017
First published
25 Mai 2017

Org. Biomol. Chem., 2017,15, 5161-5170

Isonucleotide incorporation into middle and terminal siRNA duplexes exhibits high gene silencing efficacy and nuclease resistance

Y. Ma, S. Liu, Y. Wang, Y. Zhao, Y. Huang, L. Zhong, Z. Guan, L. Zhang and Z. Yang, Org. Biomol. Chem., 2017, 15, 5161 DOI: 10.1039/C7OB01065F

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements