mRNArchitect: sequence design of mRNA medicines

Sequence design is a critical first step in the development of mRNA medicines. The primary sequence can be optimised to improve translation, stability and immunogenicity. Here, we present mRNArchitect, a software toolkit for the design and optimisation of primary mRNA sequences according to codon usage, secondary structure and manufacturability. mRNArchitect supports multiple optimisation strategies tailored for short or long expression profiles, and different clinical applications, including vaccines, cell and gene therapies. mRNArchitect is complemented by a catalogue of validated RNA elements, including UTRs, microRNA binding sites, and regulatory elements, that provide programmable, cell-type-specific control of mRNA expression. We experimentally validate mRNArchitect designs, demonstrating improvements in expression, stability, and immunogenicity, across multiple cell types and tissues compared to current design methods. mRNArchitect is provided as an experimentally validated, software package for the design and optimisation of mRNA medicines, available at: https://basefacility.org.au/software/.