Chemically modified mRNA

mRNA is a nucleic acid that plays an important role in gene expression by serving as a template for protein biosynthesis. In vitro synthesized mRNAs encoding therapeutically relevant proteins or antigens are an emerging class of medicines and vaccines. An unusual structure present at the 5′ end of mRNA molecules – the so-called 5’ cap – protects mRNAs from premature degradation by cellular enzymes and also initiates ribosome recruitment, which is necessary for protein synthesis. One of the goals of our research is to develop chemical modifications of the cap structure, further increasing translation efficiency and stability of therapeutic mRNA under cellular conditions. We have shown that carefully selected and precisely positioned modifications of mRNA cap can both stabilize mRNA in the cell and increase its translation efficiency by several fold. Assuming similar goals, we are also working on modifications to the “other” (3’) end of mRNA, the so-called poly(A) tail.

Selected publications:

https://pubs.acs.org/doi/abs/10.1021/acschembio.0c00864

https://academic.oup.com/nar/article/48/4/1607/5715811?login=true

https://pubs.acs.org/doi/abs/10.1021/jacs.8b02597

https://pubs.rsc.org/en/content/articlehtml/2017/sc/c6sc02437h

https://rnajournal.cshlp.org/content/26/12/1815.short

https://onlinelibrary.wiley.com/doi/full/10.1002/ange.201709052