Engineered probiotics platform for oral delivery of antibody as a high-compliance alternative for immune-mediated inflammatory diseases.

Abstract

Antibody-based therapies have transformed the management of immune-mediated inflammatory diseases (IMIDs), but the need for frequent injections often leads to inadequate patient adherence and suboptimal long-term disease control. To address this challenge, we develop AIDEN (aid for IMIDs: engineered EcN), an engineered probiotic platform that enables oral delivery of therapeutic antibodies using synthetic biology. In this study, we assess the efficacy of AIDEN-IL17, a variant designed to secrete single-chain variable fragments targeting interleukin-17A (IL-17A), in murine models of psoriasis and inflammatory bowel disease. AIDEN-IL17 exhibits stable gut colonization and sustained in situ antibody production, resulting in moderate reduction of systemic IL-17A levels and significant amelioration of disease symptoms. Notably, the AIDEN platform is modular and adaptable for delivering a broad range of antibody therapeutics, offering a promising, patient-friendly strategy for the treatment of IMIDs.