Complete substitution with modified nucleotides in self-amplifying RNA suppresses the interferon response and increases potency.
Nat Biotechnol
; 2024 Jul 08.
Article
in En
| MEDLINE
| ID: mdl-38977924
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Nat Biotechnol
/
Nat. biotechnol
/
Nature biotechnology
Journal subject:
BIOTECNOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
Estados Unidos
Country of publication:
Estados Unidos