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Cationic nucleic acid scavenger and uses thereof

A nucleic acid and reagent technology, applied in the field of cationic nucleic acid scavengers, which can solve problems such as interaction destruction and limiting inflammatory activity

Pending Publication Date: 2020-05-19
THE TRUSTEES OF COLUMBIA UNIV IN THE CITY OF NEW YORK
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Upon complex formation of nucleic acids with cationic nucleic acid scavengers, the interaction between nucleic acids and nucleic acid-sensing PRRs is disrupted, limiting inflammatory activity

Method used

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  • Cationic nucleic acid scavenger and uses thereof
  • Cationic nucleic acid scavenger and uses thereof
  • Cationic nucleic acid scavenger and uses thereof

Examples

Experimental program
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Effect test

example 2

[0050] Example 2: Generation of polycation-grafted nanoparticles

[0051] The cationic nanoparticles of the present invention are polycation-grafted nanoparticles comprising cationic polydopamine-grafted hectorite synthesized by dopamine-mediated surface modification of hectorite. Laponite is a synthetic phyllosilicate similar to synthetic smectic clays that degrades to non-toxic products at neutral pH. To introduce polydopamine to the surface of hectorite, dopamine was added to the alkaline solution containing hectorite. Synthetic laponite grafted with cationic polydopamine was produced by Michael addition reaction between polyethyleneimine (PEI) and polydopamine. Unreacted PEI and polydopamine were removed by centrifugation and washed repeatedly. After modification, the zeta potential of synthetic hectorite increased significantly from −40 mV to 30 mV, indicating the modification of synthetic hectorite. Synthetic hectorite can be changed to any other inorganic particle, i...

example 3

[0052] Example 3: Generation of Cationic Microparticles

[0053] The cationic particle of the present invention is a block copolymerization synthesized by self-assembly of poly(ε-caprolactone)-block-poly[2-(dimethylamino)ethyl methacrylate] (PCL-b-PDMAEMA) things. While stirring, methanol (a selective solvent for PDMAEMA) was gradually added to the THF (tetrahydrofuran) solution containing PCL-b-PDMAEMA. The solution was allowed to stand for at least 1 hour immediately after the methanol addition was complete. Subsequently, the solution was dialyzed against water for 3 days. (Wang et al., A facile way to prepare crystalline platelets of block copolymers by crystallization-drivenself-assembly, Polymer, 54(25), page 6760, 2013).

example 4

[0054] Example 4: Inhibition of Nucleic Acid Sensor Activation by Water-Soluble Dendritic Polymers

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Abstract

The present invention discloses cationic nucleic acid scavengers to effectively inhibit the activation of multiple nucleic acid sensing pattern recognition receptors (PRRs) to treat an inflammatory orimmune response which is induced by a nucleic acid through the activation of the PRRs. The cationic nucleic acid scavengers include water soluble cationic polymers, cationic nanoparticles, and cationic micro-particles, and bind the nucleic acid in a manner that is independent of the sequences, structure or chemistry of the nucleic acid.

Description

[0001] This application claims the benefit of U.S. Provisional Application No. 62 / 512,581, filed May 30, 2017, the entire contents of which are expressly incorporated herein by reference. technical field [0002] The present invention discloses a cationic nucleic acid scavenger as an anti-inflammatory agent, which is used to effectively inhibit the activation of various nucleic acid-sensing pattern recognition receptors (PRR). Cationic nucleic acid scavengers include water-soluble cationic polymers, cationic nanoparticles and cationic microparticles. Background technique [0003] The innate immune system (non-specific immune system) involves molecular, cellular and complex mechanisms used as self-protection to protect the body from harmful stimuli such as damaged cells, irritants, pathogens or endogenous stress signals. Pattern recognition receptors (PRRs) enable immune cells such as macrophages, neutrophils, natural killer cells and dendritic cells to recognize exogenous pr...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/56A61K47/59C07K14/705
CPCC07K14/705B82Y5/00A61K47/6923A61K47/6929A61K9/5031A61K31/355A61K2300/00A61K31/74
Inventor 卡姆·W·梁伟·梁波·彭
Owner THE TRUSTEES OF COLUMBIA UNIV IN THE CITY OF NEW YORK
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