Double stranded rnai agents, compositions and methods of use

Modified dsRNAi agents with TNA and MOE modifications address the stability and loading issues of traditional RNAi agents, achieving effective gene silencing and disease suppression by enhancing metabolic stability and RISC integration.

WO2026110120A1PCT designated stage Publication Date: 2026-05-28NOVARTIS AG
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Patent Information

Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
NOVARTIS AG
Filing Date
2025-11-24
Publication Date
2026-05-28

AI Technical Summary

Technical Problem

Existing RNA interference (RNAi) agents, such as short-length double-stranded RNA (dsRNA), face challenges in achieving optimal metabolic stability and efficient loading into the RNA-induced silencing complex (RISC) for effective gene silencing, which affects their proficiency in inhibiting target gene expression.

Method used

The development of double-stranded RNAi (dsRNAi) agents with specific monomer structures and chemical modifications, including threofuranosyl nucleotides (TNA) and 2'-O-methoxyethyl (MOE) modifications, to enhance metabolic stability and RISC loading, thereby improving gene silencing efficacy.

Benefits of technology

The modified dsRNAi agents demonstrate enhanced gene silencing properties, leading to durable target gene knockdown and improved RISC incorporation, effectively suppressing diseases associated with the target gene.

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Abstract

Disclosed are, inter alia, therapeutic dsRNAi agents with at least one TNA clamp on the sense strand for use in silencing a target gene in a cell or in a subject.
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Citation Information

Patent Citations

  • siRNAs WITH VINYLPHOSPHONATE AT THE 5' END OF THE ANTISENSE STRAND

    US20210147840A1

  • Therapeutic oligonucleotides comprising pyrazolotriazine nucleotide analogues

    WO2013179292A1

  • Modified double-stranded RNA agents

    WO2024073732A1

  • Modified short interfering nucleic acid (SINA) molecules and uses thereof

    WO2024097674A2