Ernie-Switcher: RNA foundation model-guided design of programmable RNA devices in a navigable landscape.

Ernie-Switcher enables RNA toehold switch sequence optimization, achieving ON/OFF expression ratios up to 35-fold in Escherichia coli while supporting feasible threshold navigability of 86.4%.

• Why it matters: Programmable RNA device design is hard due to the vast, nonlinear sequence–structure–function landscape, limiting scalable, data-driven optimization.
• What they did: The framework couples RNAErnie-derived sequence–phenotype representations, a theoretical measure of RNA landscape navigability, and biophysical constraints to keep optimization trajectories plausible.
• The result: Validation on RNA toehold switches shows a lower bound on threshold navigability of 86.4%, and experimentally optimized switches reach up to 35-fold ON/OFF expression in Escherichia coli, enabling scalable engineering of high-performance RNA devices.