Issue 36, 2023, Issue in Progress

Non-terminal conjugation of small interfering RNAs with spermine improves duplex binding and serum stability with position-specific incorporation

Abstract

The conjugation of small interfering RNAs (siRNAs) has been studied using lipid and ligand conjugates for efficient delivery. However, most conjugates have been inserted at the terminal position; very few have been inserted at non-terminal positions. Herein, we synthesized a 4′-C-propyllevulinate-2′-O-methyluridine analog for non-terminal conjugation of spermine into the passenger strand of siRNA. Solid-phase oligonucleotide synthesis using this analog was successful, with the conjugation of one or two spermine molecules. The siRNAs conjugated with spermine displayed improved thermodynamic stability and resistance against nucleases, which depended on the site of conjugation in each case. Circular dichroism spectroscopy revealed that the A-type helical structure of the RNA duplex was not altered by these modifications. However, the gene-silencing activity of conjugated siRNAs was reduced and further decreased when the number of spermine molecules was increased. Hence, this work supplies valuable information and provides scope for the further development of drug-delivery systems through non-terminal conjugation.

Graphical abstract: Non-terminal conjugation of small interfering RNAs with spermine improves duplex binding and serum stability with position-specific incorporation

Supplementary files

Article information

Article type
Paper
Submitted
21 Jul 2023
Accepted
17 Aug 2023
First published
23 Aug 2023
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2023,13, 25169-25181

Non-terminal conjugation of small interfering RNAs with spermine improves duplex binding and serum stability with position-specific incorporation

K. Koyasu, A. Chandela and Y. Ueno, RSC Adv., 2023, 13, 25169 DOI: 10.1039/D3RA04918C

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