# Synthesis of siRNAs containing carbocyclic nucleotides and the role of cyclopentane conformation in RNAi activity

## TL;DR

Researchers modified siRNAs with carbocyclic nucleotides to improve gene silencing in cells and mice.

## Contribution

A new method for enhancing RNAi activity through carbocyclic nucleotide modifications at siRNA termini.

## Key findings

- Carbocyclic nucleotides at siRNA 5′ ends improved gene silencing compared to unmodified siRNAs.
- 3′-O-methyl carbocyclic analogues showed lower activity than other modifications.
- Modifications were effective in both cell and mouse models.

## Abstract

5′-(E)- and 5′-(Z)-vinylphosphonate carbocyclic DNA and 5′-(E)-vinylphosphonate 2′- and 3′-O-methyl carbocyclic RNAs were incorporated at 5′ termini of antisense strands of small interfering RNAs. All but the 3′-O-methyl carbocyclic analogue resulted in gene silencing activity better than the siRNA lacking a 5′ phosphate in cells and in mice.

5′-(E)- and 5′-(Z)-vinylphosphonate carbocyclic DNA and 5′-(E)-vinylphosphonate 2′- and 3′-O-methyl carbocyclic RNAs were incorporated at 5′ termini of antisense strands of small interfering RNAs.