The 5′ Cap Epitranscriptome and Beyond: Natural and Engineered 5′ Cap Modifications for Optimizing mRNA Therapeutics and Functional Studies
Greta Charlotte Dahm, Melissa Pieper, Helena Schepers, Andrea Rentmeister
TL;DR
This paper explores how modifying the 5′ cap of mRNA can improve its stability, reduce immune response, and enhance translation for better therapeutic applications.
Contribution
The paper introduces both natural and engineered 5′ cap modifications as tools to optimize mRNA properties and study mRNA function.
Findings
Natural 5′ cap modifications influence mRNA translation, stability, and immunogenicity.
Engineered non-natural 5′ cap modifications can enhance mRNA properties and provide reactive handles for functional studies.
5′ cap modifications can be introduced using enzymes or chemical synthesis methods.
Abstract
Eukaryotic mRNAs made by in vitro transcription have emerged as medical modalities for vaccination and protein replacement therapy. The 5′ cap is an essential feature of eukaryotic mRNAs providing stability, reducing immunogenicity, and serving as starting point for translation initiation. The “cap epitranscriptome” comprises several natural 5′ cap modifications that can impact mRNA interactions and fate. Manipulating this privileged structure provides a powerful handle to optimize mRNA properties and to build a toolbox for investigating and controlling mRNA‐related processes. In this article, the impact of natural 5′ cap modifications on mRNA translation, immunogenicity, and stability is highlighted. Then, it is shown how non‐natural 5′ cap modifications have been used to manipulate and optimize various mRNA properties. Finally, non‐natural modifications can equip mRNA with reactive…
Click any figure to enlarge with its caption.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8Peer Reviews
No public reviews on file for this paper yet. If you reviewed it on a platform where reviews are public (OpenReview, ICLR, NeurIPS, ICML), you can paste yours below so the community can read it here.
Videos
No videos yet. Explain this paper in a talk, walkthrough, or lecture? Add one.
Taxonomy
TopicsRNA Interference and Gene Delivery · RNA Research and Splicing · RNA and protein synthesis mechanisms