CleanCap M6 inhibits decapping of exogenously delivered IVT mRNA
Zachary F. Mandell, Andrew Ujita, Jordana M. Henderson, Anthony Truong, Christoph Vo, Farinaz Rezvani, Nona Abolhassani, Alexandre Lebedev, Chunping Xu, Inna Koukhareva, Stephanie Ramos, Kate E. Broderick, Benjamin H. Hudson, Jeff Coller
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 m7 G 3'OMe ppp m6 A 2′OMe pG, 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.