A Bioengineered Probiotic for the Oral Delivery of a Peptide Kv1.3 Channel Blocker To Treat Rheumatoid Arthritis

Authors

Yuqing Wang
Duolong Zhu
Laura C Ortiz-Velez
Jacob L Perry
Michael W Pennington
Joseph M Hyser
Robert A Britton
Christine Beeton

Publication Date

1-10-2023

Journal

Proceedings of the National Academy of Sciences of the United States of America

DOI

10.1073/pnas.2211977120

PMID

36595694

PMCID

PMC9926172

PubMedCentral® Posted Date

1-3-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Rats, Humans, Animals, Kv1.3 Potassium Channel, Peptides, Arthritis, Rheumatoid, Inflammation, Probiotics, Potassium Channel Blockers, synthetic biology, Kv1.3 channel, drug delivery

Abstract

New therapeutics that combine efficacy with limited side effects and can be delivered noninvasively are needed to adequately treat patients with rheumatoid arthritis (RA) and other autoimmune diseases. Kv1.3 channel-expressing CCR7− effector memory T (TEM) lymphocytes are significant players in the pathogenesis of multiple autoimmune diseases, and blocking Kv1.3 reduces disease severity in rat models of RA and patients with plaque psoriasis. However, peptide therapeutics require repeated injections, reducing patient compliance. We used a bioengineered Lactobacillus reuteri as an oral delivery method of a Kv1.3 blocker for immunomodulation in rat models of atopic dermatitis and RA. This study demonstrates a novel approach for the noninvasive delivery of peptide-based therapeutics for the oral treatment of chronic inflammatory diseases.

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