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

## TL;DR

Scientists created an engineered probiotic platform called AIDEN to deliver antibodies orally for treating inflammatory diseases, improving patient compliance.

## Contribution

AIDEN is a novel engineered probiotic platform enabling oral delivery of therapeutic antibodies for immune-mediated inflammatory diseases.

## Key findings

- AIDEN-IL17 colonizes the gut and produces functional anti-IL-17A scFvs, reducing systemic IL-17A levels.
- AIDEN-IL17 significantly ameliorates symptoms in psoriasis and inflammatory bowel disease murine models.
- The modular AIDEN platform can be adapted for various antibody therapeutics.

## 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.

•Construct AIDEN-IL17 for in situ on-demand production of anti-IL-17A scFvs•AIDEN-IL17 secretes functional scFvs for prolonged IL-17A neutralization•AIDEN-IL17 offers a cost-effective and convenient alternative for IMIDs

Construct AIDEN-IL17 for in situ on-demand production of anti-IL-17A scFvs

AIDEN-IL17 secretes functional scFvs for prolonged IL-17A neutralization

AIDEN-IL17 offers a cost-effective and convenient alternative for IMIDs

Liu et al. develop an engineered probiotics platform (AIDEN) to overcome the challenge of inadequate patient compliance for lifelong management of immune-mediated inflammatory diseases. AIDEN-IL17, a variant targeting IL-17A, exhibits moderate yet sustained neutralization of IL-17A in murine models and controls inflammation progression in psoriasis and colitis.