Complete substitution with modified nucleotides in self-amplifying RNA suppresses the interferon response and increases potency.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38977924.
- Also identified by DOI 10.1038/s41587-024-02306-z and PMC identifier 11707045.
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Abstract
The use of modified nucleotides to suppress the interferon response and maintain translation of self-amplifying RNA (saRNA), which has been achieved for mRNA, has not yet succeeded. We identify modified nucleotides that, when substituted at 100% in saRNA, confer innate immune evasion and robust long-term protein expression, and when formulated as a vaccine, protect against lethal SARS-CoV-2 challenge in mice. This discovery advances saRNA therapeutics by enabling prolonged protein expression at low doses.
Medical subject headings
- SARS-CoV-2
- COVID-19
- Interferons
- RNA, Viral
- Nucleotides
- COVID-19 Vaccines