Conjugated Polycationic Polymer Sequestering Nucleic Acids

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current methods fail to effectively address the excessive levels of circulating nucleic acids in diseases like autoimmune disorders and radiation exposure, as they often trigger inflammatory responses and compromise the immune system's ability to combat infections.

Innovation Solution

Conjugated polycationic polymers that bind and sequester nucleic acids, reducing their concentration in bodily fluids and preventing activation of nucleic acid-sensing Toll-like receptors, thereby mitigating inflammation without impairing the immune response to pathogens.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If conventional methods are used to eliminate circulating nucleic acids, then nucleic acid levels are reduced, but inflammatory responses are triggered and immune system function is compromised

Engineering Contradiction:
Improvecirculating nucleic acid levelsVSAvoidinflammatory response and immune compromise
Core Design Contradiction:
Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent uses polycationic polymers as intermediary agents that bind to circulating nucleic acids through electrostatic interactions. These polymers act as mediators that sequester nucleic acids in a non-inflammatory manner, preventing their interaction with nucleic acid-sensing receptors while avoiding the inflammatory responses triggered by conventional elimination methods

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention changes the physical-chemical parameters of nucleic acid handling by using cationic polymers with specific charge densities and molecular weights. This parameter change allows for gentle sequestration rather than aggressive elimination, maintaining immune tolerance while reducing pathogenic nucleic acid levels

Inventive Principle:
Principle #35Parameter changes

2Object-affected harmful factors

If nucleic acid scavengers are used to reduce aberrant inflammation, then inflammation is ameliorated, but the mechanism and selectivity need further deciphering for clinical translation

Engineering Contradiction:
Improveaberrant inflammationVSAvoidmechanism complexity and clinical translation barrier
Core Design Contradiction:
Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The patent applies local quality by designing polymers with specific cationic charge distributions and functional group placements. This localized functional differentiation allows selective binding to pathogenic nucleic acids while preserving beneficial immune interactions, thereby reducing aberrant inflammation without compromising overall immune function

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The polycationic polymers exhibit multi-functionality by simultaneously binding nucleic acids, modulating immune responses, and reducing inflammation. This universal action simplifies the therapeutic approach compared to multiple separate interventions, facilitating clinical translation while maintaining mechanistic clarity

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Reliability

If current drugs are used to treat diseases with excessive nucleic acids, then treatment is provided, but facile chemical modification and alternative approaches are limited

Engineering Contradiction:
Improvetreatment effectivenessVSAvoidchemical modification flexibility
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent segments the therapeutic approach by using modular polycationic polymer structures that can be independently synthesized and characterized. This segmentation allows facile chemical modification of polymer generations, branch densities, and terminal functional groups, enabling flexible optimization for different disease states while maintaining reliable treatment effectiveness

Inventive Principle:
Principle #1Segmentation

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The polymers effectively reduce inflammatory mediators and autoantibody levels, improving autoimmune disease outcomes and enhancing survival in radiation exposure scenarios without suppressing the immune system's ability to fight infections.

Implementation Method 1

conjugated polycationic polymers that bind and sequester nucleic acids, reducing their concentration in bodily fluids

Methodology Applied
Scientific EffectElectrostatic interaction: Electrostatics

Implementation Method 2

a detectable label; and a crosslinker, wherein the crosslinker links the detectable label and the focal point of the dendron

Methodology Applied
Scientific EffectDetectable label:

Data Source

PatentUS20210000981A1Conjugated polycationic polymers, methods of using the same and methods of treating autoimmune diseases, infectious diseases and acute radiation exposure
Publication Date: 2021.01.07 DUKE UNIV
  • US20210000981A1 patent drawing
  • US20210000981A1 patent drawing
  • US20210000981A1 patent drawing

AI summary

Disclosed herein are polycationic polymers and methods of using the same. The polycationic polymer comprises a dendrimer or dendron, the dendrimer or the dendron comprising a focal point, a plurality of cationic termini, and a branched cationic polymer between the focal point and the plurality of cationic termini. Also disclosed polycationic polymers further comprising a detectable label; and a crosslinker, wherein the crosslinker links the detectable label and the focal point of the dendron. The resulting conjugated polycationic polymers may be used in tracking methods of methods of treating disease. Methods of using polycationic polymers to treat autoimmune diseases, infectious diseases and acute radiation syndrome are also disclosed.