A stability boost for in vivo Cell and Gene Therapy

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!