ARCADE: Controllable Codon Design from Foundation Models via Activation Engineering

ARCADE is a controllable multi-objective codon design framework that leverages pretrained genomic language models and extends activation engineering — originally developed for controllable text generation — to steer continuous-valued biological metrics. By deriving semantic steering vectors in the model’s activation space, ARCADE directly controls properties such as Codon Adaptation Index (CAI), Minimum Free Energy (MFE), and GC content, enabling programmable biological sequence design for applications including mRNA vaccines and gene therapies.

Recommended citation: Li J, Lai HS, Liang L, Du S, Tang S, Kingsford C. ARCADE: Controllable Codon Design from Foundation Models via Activation Engineering. bioRxiv. 2025. doi:10.1101/2025.08.19.668819
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