CleanCap M6 inhibits decapping of exogenously delivered IVT mRNA.

ABSTRACT: Co-transcriptional capping allows exogenous mRNAs to yield robust protein expression. Identifying additional mRNA modifications that further boost protein output will be crucial for developing more efficacious mRNA therapies. Using in vitro approaches, we found that the co-transcriptional cap analog ^m7G_3'OMeppp^m6A_2'OMepG, CleanCap M6, resists enzymatic decapping and that this decreased susceptibility to decapping correlated with substantially increased protein expression in vivo compared to mRNAs capped using existing industry standards.

SUBMITTER: Mandell ZF 

PROVIDER: S-EPMC11835620 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature