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Significance Pathological inflammation resulting from autoimmune, inflammatory, and infectious diseases remains the major cause of morbidity and mortality around the world. We explored the utility of nucleic acid-binding polymers to limit pathological activation of the innate immune response by scavenging nucleic acid-containing debris. We evaluated such polymers following local and systemic delivery for treatment of cutaneous and systemic lupus erythematosus in mice and observed dramatic therapeutic benefit. Remarkably, such treatment does not limit the ability of lupus-prone mice to combat influenza infection. Thus, by selectively targeting activators of the pathogenic immune response rather than the effectors of the innate immune system, nucleic acid scavengers are able to limit pathological inflammation without compromising one’s ability to fight a viral infection.

Scavenging nucleic acid debris to combat autoimmunity and infectious disease