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September 10, 2025eLifeOpen Access

Cap-independent co-expression of dsRNA-sensing and NF-κB pathway inhibitors enables controllable self-amplifying RNA expression with reduced immunotoxicity

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Authors

TLTony K.Y. LimARAnne RitouxLPLuke W Paine

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Overview

Engineered immune-evasive saRNA reduces innate immune responses, enabling safer gene expression in cells implicated in joint diseases.

Key Points

  • Immune-evasive saRNA enables sustained transgene expression without external immunosuppressants.
  • This system reduces cytotoxicity and antiviral cytokine secretion significantly in mouse fibroblast-like synoviocytes.
  • Cap-independent translation allows co-expression of inhibitors targeting key innate immune pathways.
  • Offering concentration-dependent control and on-demand termination, this platform advances future saRNA therapeutics.

Cite This Study

Lim et al. (2025) studied this question.

synapsesocial.com/papers/68c1d97154b1d3bfb60facfbhttps://doi.org/10.7554/elife.105978.3
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Cap-independent co-expression of dsRNA-sensing and NF-κB pathway inhibitors enables tunable self-amplifying RNA expression with reduced immunotoxicity2025 · 1 citations
  2. 2Non-immunogenic and reversible transgene expression using self-amplifying RNA2024
  3. 3The Interplay Between Therapeutic Self-Amplifying RNA and the Innate Immune System: Balancing Efficiency and Reactogenicity2025
  4. 4A Novel Self‐Amplifying mRNA with Decreased Cytotoxicity and Enhanced Protein Expression by Macrodomain Mutations2024 · 15 citations
  5. 5Engineering drug-responsive replication machinery for precise control of self-amplifying RNA2026 · 3 citations