Nucleic Acid Scavengers as Novel Regulators of Autoimmunity and Viral Infection

Abstract

Nucleic acids released from dead and dying cells can be recognized as damage-associated molecular patterns (DAMPs) or pattern-associated molecular patterns (PAMPs) by the innate immune system. Unregulated activation of the innate immune response by such endogenous molecules can stimulate pathological inflammation resulting autoimmune disease. Therapeutic efforts have been made to block this inflammation directly by targeting a class of pattern recognition receptors (PRRs), known as Toll-like receptors (TLRs) that recognize such DAMPs and PAMPs, or their downstream signaling molecules. Unfortunately, such therapeutic approaches can suppress immune system and its ability to fight off pathogens. There is a great need for novel therapies that can block this aberrant inflammation prior to TLR and immune recognition, thus allowing normal immune function. A novel class of Nucleic Acid Scavenging Polymers (NASPs) were examined for their ability to do just that. Previously shown to act as nucleic acid scavengers with the ability to neutralize agonists of TLRs NASPs are evaluated for their ability to act prior to TLR activation. Thus, not incurring the non-specific immune suppression evident in other autoimmune therapeutic strategies. Furthermore, NASPs do not limit an animal’s ability to combat viral infection, but rather their administration improves survival when animals are challenged with lethal doses of influenza. The studies outlined in this document suggest that molecules that scavenge extracellular nucleic acids potentially represent promising therapeutic agents to control pathological inflammation associated with a wide range of autoimmune and infectious diseases.