Double stranded rnai agents, compositions and methods of use
Modified dsRNAi agents with specific nucleotide sequences and chemical modifications address the challenges of metabolic stability and RISC loading, achieving improved gene silencing efficacy in both animal and human cell models.
Patent Information
- Application Number
- PCT/IB2025/057025
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2024-11-25
- Filing Date
- 2025-07-10
- Publication Date
- 2026-01-15
AI Technical Summary
Existing RNAi agents face challenges in optimizing the design of double-stranded RNA (dsRNA) for effective gene silencing, particularly in terms of metabolic stability and loading efficiency into the RNA-induced silencing complex (RISC), which affects their gene-silencing properties for therapeutic applications.
The development of double-stranded RNAi (dsRNAi) agents with specific monomer sequences and chemical modifications, such as 2′-O-methoxyethyl (MOE) and 2′-fluoro (2′-F) nucleotides, along with phosphorothioate linkages, to enhance metabolic stability and RISC loading, thereby improving gene silencing efficacy.
The modified dsRNAi agents demonstrate improved half-life and enhanced gene silencing capabilities, leading to durable target gene knockdown and RISC incorporation, as evidenced by significant reductions in target mRNA and protein levels in both animal and human cell models.