Vault Packaging Dynamics: Cargo Loading Stabilizes MVP Conformation for High-Payload Cytokine Delivery in Cancer Therapy

IL-2–packaged human vaults show cryoEM-resolved D39-symmetric barrels at 2.79 Å that are enlarged and distorted, with cargo loading stabilizing MVP conformation.

• Why it matters: Optimizing vault-based cancer and immune therapeutics requires knowing how cargo loading changes assembly heterogeneity and MVP dynamics to support high-payload delivery.
• What they did: Using integrative cryoEM, cryoET, and CDMS on yeast-produced empty and IL-2–packaged vaults, the study quantified IL-2–INT populations centered near 100 and 400 molecules per vault, with a maximum of ~660.
• The result: Empty vaults are conformationally flexible for initial cargo entry, while loading stabilizes and condenses cargo, yielding ~150–600 IL-2 molecules per vault and enabling quantitative engineering of delivery vehicles.

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