siRNA sequence-independent modification formats for reducing off-target phenotypic effects in RNAi, and stabilized forms thereof

US10329564B2 · kind B2 · utility

Assignee

• Applied Biosystems, LLC · US

Inventors

• Nitin Puri · Austin, US
• Irudaya Charles · Austin, US
• Susan Magdaleno · Austin, US
• Alexander Vlassov · Austin, US
• Christopher Burnett · Austin, US

Key dates

• Filing date: Sep 5, 2017
• Grant date: Jun 25, 2019
• Expiry date: Oct 14, 2037

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12N2320/53
• WIPO field: Biotechnology
• WIPO sector: Chemistry

Abstract

Modification formats having modified nucleotides are provided for siRNA. Short interfering RNA having modification formats and modified nucleotides provided herein reduce off-target effects in RNA interference of endogenous genes. Further modification formatted siRNAs are demonstrated to be stabilized to nuclease-rich environments. Unexpectedly, increasing or maintaining strand bias, while necessary to maintain potency for endogenous RNA interference, is not sufficient for reducing off-target effects in cell biology assays.