Novel Nucleic Acid Binding Polymers as Anti-Inflammatory Agents
Aberrant inflammation contributes to a variety of serious medical conditions, including autoimmune diseases such as multiple sclerosis, overwhelming infections such as sepsis, and pathological wound healing. Extracellular nucleic acids can contribute to ongoing inflammation by activating Toll-Like Receptors (TLR’s). Neutralizing these pro-inflammatory extracellular nucleic acids could prevent pathological inflammation by preventing TLR activation
Cationic nucleic acid binding polymers capable of neutralizing extracellular nucleic acids were identified through screening a combinatorial library. Nucleic acid binding cationic polymers poly(β-amino ester), disulfide containing poly(βamido-amine) and poly(β-hydroxyl amine) were able to specifically inhibit TLR 9 activation by forming stable polyplexes with extracellular pro-inflammatory nucleic acids. Furthermore, the screening method used ensured that these polymers had minimal effects on other TLR’s, had minimal cytotoxicity, and were not taken up by the cells. The inventors were able to demonstrate that cationic nucleic acid binding polymers can inhibit TLR activation when administered directly to the cell or cell medium, or when administered to a human subject.
The neutralization of pro-inflammatory nucleic acids has a variety of applications related to anti-inflammatory action, including, but not limited to, the following:
- Systemic administration for autoimmune conditions (eg. systemic lupus erythematosus, rheumatoid arthrtitis, multiple sclerosis, inflammatory bowel disease)
- Systemic administration for chronic diseases characterized by pathological inflammation (eg. chronic obstructive pulmonary disease, obesity, cardiovascular disease, diabetes)
- Systemic administration for infectious diseases
- Systemic administration for patients undergoing chemotherapy or other treatments resulting in cell death or nucleic acid-based inflammation
- Topical administration for burns or chronic wounds
- The screening method can identify polymers that specifically target nucleic acids that trigger TLR9 activation, while maintaining minimal cytotoxicity
- Nucleic-acid binding polymers have broad clinical applications in situations where pathological inflammation is mediated by nucleic acids
Duke File (IDF) Number
- Sullenger, Bruce
- Holl, Eda
- Juwarker, Hemraj
- Patent Number: PCT/US2014/033509
- Title: ANTI-INFLAMMATORY AGENTS AND METHODS OF USING THE SAME
- Country: PCT (Not Applicable)
For more information please contact
- Gopalakrishnan, Karthik
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