July 15, 2025Open Access

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

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Novel approach demonstrates sustained gene expression in fibroblast-like synoviocytes, suggesting immune evasion can improve gene therapy outcomes.

The strategy incorporates immune suppression within self-amplifying RNA, enhancing transgene expression without external inhibitors.
In mouse fibroblast-like synoviocytes, this method significantly reduces cytotoxicity and cytokine release.
Cap-independent translation allows the saRNA to bypass immune-triggered shutdown, promoting sustained gene expression.
These findings pave the way for safer gene therapies that minimize systemic immune responses and treatment complexity.

Lim et al. (2025) studied this question.

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July 15, 2025Open Access

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Authors

Novel approach demonstrates sustained gene expression in fibroblast-like synoviocytes, suggesting immune evasion can improve gene therapy outcomes.

The strategy incorporates immune suppression within self-amplifying RNA, enhancing transgene expression without external inhibitors.
In mouse fibroblast-like synoviocytes, this method significantly reduces cytotoxicity and cytokine release.
Cap-independent translation allows the saRNA to bypass immune-triggered shutdown, promoting sustained gene expression.
These findings pave the way for safer gene therapies that minimize systemic immune responses and treatment complexity.

Lim et al. (2025) studied this question.

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