Chemical modification of uridine modulates mRNA-mediated proinflammatory and antiviral response in primary human macrophages.

ABSTRACT: In vitro transcribed (IVT)-mRNA has been accepted as a promising therapeutic modality. Advances in facile and rapid production technologies make IVT-mRNA an appealing alternative to protein- or virus-based medicines. Robust expression levels, lack of genotoxicity, and their manageable immunogenicity benefit its clinical applicability. We postulated that innate immune responses of therapeutically relevant human cells can be tailored or abrogated by combinations of 5'-end and internal IVT-mRNA modifications. Using primary human macrophages as targets, our data show the particular importance of uridine modifications for IVT-mRNA performance. Among five nucleotide modification schemes tested, 5-methoxy-uridine outperformed other modifications up to 4-fold increased transgene expression,

SUBMITTER: Moradian H 

PROVIDER: S-EPMC8807976 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature