A DNA Origami Device Spatially Controls CD95 Signalling to Induce Immune Tolerance in Rheumatoid Arthritis

Overview

Journal Nat Mater

Date 2024 Apr 9

PMID 38594486

Authors

Ling Li

Jue Yin

Wen Ma

Longguang Tang

Jianhua Zou

Linzi Yang

Ting Du

Yi Zhao

Lianhui Wang

Zhen Yang

Chunhai Fan

Jie Chao

Xiaoyuan Chen

Affiliations

Soon will be listed here.

Abstract

DNA origami is capable of spatially organizing molecules into sophisticated geometric patterns with nanometric precision. Here we describe a reconfigurable, two-dimensional DNA origami with geometrically patterned CD95 ligands that regulates immune cell signalling to alleviate rheumatoid arthritis. In response to pH changes, the device reversibly transforms from a closed to an open configuration, displaying a hexagonal pattern of CD95 ligands with ~10 nm intermolecular spacing, precisely mirroring the spatial arrangement of CD95 receptor clusters on the surface of immune cells. In a collagen-induced arthritis mouse model, DNA origami elicits robust and selective activation of CD95 death-inducing signalling in activated immune cells located in inflamed synovial tissues. Such localized immune tolerance ameliorates joint damage with no noticeable side effects. This device allows for the precise spatial control of cellular signalling, expanding our understanding of ligand-receptor interactions and is a promising platform for the development of pharmacological interventions targeting these interactions.

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