Epigenetic modification of RNA, the RNA analog of the DNA epigenome, has been observed for over 40 years and is known as the epitranscriptome. Messenger RNAs (mRNAs) in particular are post-transcriptionally modified, obtaining base modifications as well as 2ʹ methylation of sugars near the 5ʹ cap. Cap modifications identify the mRNA as self rather than foreign, and modulate stability, translation, decapping, and regulation of mRNAs. Tools to effectively mimic the epitranscriptome have not existed until now. With the development of a co-transcriptional capping method called CleanCap®, mRNAs with each of the four different types of 5ʹ caps can be produced. In this article, we describe this new technology and its implications for mRNA therapeutics.