Abstract
mRNA medicine is a new and rapidly developing field in which the delivery of genetic information in the form of mRNA is used to direct therapeutic protein production in humans. This approach, which allows for the quick and efficient identification and optimization of drug candidates for both large populations and individual patients, has the potential to revolutionize the way we prevent andtreat disease. A key feature of mRNA medicines is their high degree of designability, although the design choices involved are complex. Maximizing the production of therapeutic proteins from mRNA medicines requires a thoroughunderstanding of how nucleotide sequence, nucleotide modification and RNA structure interplay to affect translational efficiency and mRNA stability. In this Review, we describe the principles that underlie the physical stability and biological activity of mRNA and emphasize their relevance to the myriad considerations that factor into therapeutic mRNA design.
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