MESSI: a discrete diffusion model for generative protein deimmunization of designed therapeutics
LeoTZ03 · x · 2026-10-19
Researchers introduce MESSI, a discrete diffusion model for generative protein deimmunization.
Background: generative protein design is transforming macromolecular drugs, but de novo designed therapeutics can still be hindered by immunogenicity in the clinic (anti-drug antibodies). MESSI generates sequence variants with minimal predicted immune risk while preserving function, using a lookahead/feedback denoising process guided by an immunogenicity predictor — the figure walks through masked-sequence denoising across depths plus the CD4+ T cell activation / anti-drug antibody mechanism it aims to avoid.
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