One of the longstanding challenges with in vivo mRNA therapeutics is stability. Even with today’s best optimizations—nucleoside modifications, refined UTRs, improved poly-A tails, and codon optimization—linear mRNA delivered via LNPs is typically degraded within hours to a day across most tissues.
A newly published study takes inspiration from viral genomes, which have evolved sophisticated ways to protect their RNA inside host cells. The researchers identified a novel element, A7, that dramatically enhances mRNA stability across cell types, delivery modalities, sequence contexts, and modification strategies. Impressively, A7-engineered linear mRNA reaches stability comparable to circular RNA, while achieving higher translation efficiency.
Pairing sustained expression like this with precise in vivo targeting — the focus of what we’re building at Tiva.Bio — moves us even closer to unlocking in vivo CAR-T and in vivo gene editing for patients.
Exciting times ahead for the field.
RNA stability enhancers for durable base-modified mRNA therapeutics