Nucleic acid scavengers to reduce inflammation

This technology is a set of compounds that remove pathogenic nucleic acids to counteract noninfectious inflammatory responses.

Unmet Need: Method for inhibiting pathogenic inflammation without harming normal immune system function

Inflammation is a complex biological process orchestrated by the immune system in response to harmful stimuli, such as tissue damage or infection. Pattern recognition receptors (PRRs), including Toll-like receptors (TLRs), are responsible for initiating the inflammatory response, as they recognize and respond to various harmful stimuli to protect the body. However, inappropriate activation of PRRs can lead to a number of diseases, including autoimmune diseases, transplant immunity, and excessive inflammation. Nucleic acids from host cells or intracellular microorganisms are one set of molecules capable of initiating and perpetuating a noninfectious inflammatory response through activation of PRRs. While several drugs capable of targeting and blocking these receptors have been developed, they all attenuate normal immune function. As such, there is a need for therapeutics that can inhibit pathogenic inflammation without directly inhibiting PRRs.

The Technology: Nucleic acid scavengers remove extracellular nucleic acid molecules to reduce inflammation

This technology describes several cationic compounds capable of binding to and scavenging extracellular nucleic acids, which are known to initiate pathogenic immune responses. Unlike currently available therapeutics, the cationic agents have a strong affinity for the negatively-charged phosphate backbone of nucleic acids and are able to inhibit noninfectious inflammatory responses indirectly, thereby leaving normal immune function intact. This technology describes three different cationic agents of varying size that scavenge nucleic acids: water-soluble polymers, nanoparticles, and larger microparticles. These compounds have the advantage of a large surface area and high charge density for improved nucleic acid binding activity, and they are large enough to evade cellular internalization for continuous scavenging at the site of inflammation.

This technology has been validated for its anti-inflammatory function in vitro and for low toxicity in vivo in a mouse model.

Applications:

• Therapeutic for removing pathogenic nucleic acids without interfering with normal immune function
• Prevention of post-injury inflammation and transplant immunity
• Diagnostic assay for detecting nucleic acids as biomarkers of disease
• Treatment of rheumatoid arthritis, psoriasis, and other autoimmune diseases
• Research tool for the identification and purification of specific nucleic acids
• Research tool for studying the role of nucleic acids in other diseases

Advantages:

• Safe and effective method to reduce pathogenic inflammation
• Bypasses immune system receptors leaving normal function intact
• Can target any disease initiated by nucleic acids without the need for in-depth knowledge of receptor ligands
• Targeted approach allows lower dose and less toxicity
• Different types of cationic nucleic acid scavengers allow therapeutic to be tailored to specific tissues or diseases

Lead Inventor:

Kam Leong, Ph.D.

Patent Information:

Patent Status

Related Publications:

• Zhang Y, Phua K, Chan HF, Sullenger B, Leong KW. “Immobilization of nucleic acid binding polymers as anti-inflammatory agent in autoimmunity” J Control Release 2015 Sep; 213: e136.

• Lee J, Sohn JW, Zhang Y, Leong KW, Pisetsky D, Sullenger BA. “Nucleic acid-binding polymers as anti-inflammatory agents” Proc Natl Acad Sci USA. 2011 Aug; 108(34): 14055-14060.

Tech Ventures Reference:

• IR C17078

• Licensing Contact: Joan Martinez