Bioinformatic Design of long mRNA – Unlocking the 8-12kb Frontier
- Long mRNAs (8-12kb) unlock new therapeutic modalities impossible with 2-5kb constructs (large protein replacement, gene editing, self-amplifying RNA, polycistronic mRNA, tissue targeting, etc.)
- Designing longer mRNA sequences requires not only greater computational power but also new, scalable algorithms AND the integration of stringent manufacturing constraints (repeat sequences, dsRNA-forming structures, plasmid instability, etc.)
- While human cells naturally produce long mRNAs, the in vitro transcription (IVT) process scales poorly with increasing mRNA length. Is it time to mimic eukaryotic cells to enable the production of longer mRNAs?