HMGB1-targeted anti-inflammatory rBox A gene therapy for viral airway infections and systemic inflammatory disease models.

A non-replicating adenoviral vector delivering recombinant HMGB1 Box A reduces inflammation in multiple HMGB1-driven disease models.

• Why it matters: Elevated extracellular HMGB1 levels are linked to disease severity in inflammatory conditions, but clinical translation of HMGB1 antagonists faces challenges like dosing and off-target effects.
• What they did: Researchers engineered an adenoviral vector that produces recombinant Box A in response to inflammation, and tested its delivery and efficacy across infectious and non-infectious inflammation models.
• The result: Therapeutic administration of the vector provided significant protection and inflammation reduction, suggesting its potential as a broad-spectrum, host-directed gene therapy for HMGB1-mediated diseases.