DNA Scavenging Biomaterials for Treatment of Autoimmune Disease: A Review.

Abstract

Cell-free DNA (cfDNA) has emerged as an important mediator of autoimmune inflammation and a promising therapeutic target for restoring immune homeostasis. Excessive cfDNA activates nucleic acid-sensing pathways such as Toll-like receptor 9 (TLR9) and stimulator of interferon genes (STING), which drive proinflammatory responses and worsen tissue injury. Researchers have developed various biomaterial-based cfDNA scavengers to neutralize or eliminate pathogenic cfDNA. This review summarizes recent advances in the design, functional mechanisms, and therapeutic potential of cfDNA-clearing materials for autoimmune diseases. Representative systems-including cationic polymers, enzyme-based platforms, and metal-organic framework-are discussed in terms of their structural features, cfDNA-binding, and immunomodulatory effects. Particular attention is given to how these materials suppress cfDNA-triggered inflammatory signaling and alleviate disease manifestations in rheumatoid arthritis and other autoimmune disease models. Finally, we discuss challenges for clinical translation, including biosafety, target specificity, in vivo stability, and the lack of evaluation standards. Overall, cfDNA-scavenging biomaterials offer a promising platform for modulating aberrant inflammation in autoimmune diseases.