Kaiyi Jiang

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1. 2d
   Princeton team launches MESSI, a diffusion model for deimmunizing protein drugs

   Kaiyi Jiang, an assistant professor in Princeton University's bioengineering department, and collaborators posted a preprint, "Protein Deimmunization with a Generative Diffusion Model," introducing MESSI, a generative protein design model. Building on inverse-folding approaches such as ProteinMPNN, MESSI adds an MHC-II presentation-related immunogenicity risk predictor and a "Lookahead–Feedback" mechanism that samples candidate sequences mid-diffusion, then re-masks and re-predicts high-risk positions. The team tested designs on three proteins — luciferase, a PD-1 binding protein and urate oxidase — reporting that some candidates had predicted epitope counts reduced to zero while retaining activity, with the best urate oxidase variant about 2.7 times as active as the original protein. The authors note that whether these designs actually trigger weaker immune responses in humans remains unproven.

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