Modified MicroRNA Compositions for Nervous System Dysfunction

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Solution Overview

Problem

Current therapies for nervous system dysfunction, such as neurodegenerative disorders and spinal cord injuries, face challenges in effectively delivering microRNAs due to biological instability and poor cellular uptake, limiting their therapeutic potential.

Innovation Solution

Development of microRNA compositions, including modified miRNA-7, miRNA-153, miRNA-34b, miRNA-34c, and miRNA-155, with deoxyribonucleotide modifications, delivered via viral vectors or nanoparticles to enhance therapeutic efficacy in treating nervous system dysfunction.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If microRNA is used for therapeutic treatment of nervous system dysfunction, then therapeutic potential is improved, but biological stability and cellular uptake are insufficient

Engineering Contradiction:
Improvetherapeutic potentialVSAvoidbiological stability
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent applies parameter changes by modifying the chemical structure of microRNA through deoxyribonucleotide substitutions at specific positions (5' end of guide strand, 3' end of passenger strand). These structural parameter changes enhance biological stability and cellular uptake while maintaining therapeutic function, directly resolving the contradiction between therapeutic potential and biological stability

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates composite microRNA structures by combining modified guide and passenger strands with specific deoxyribonucleotide sequences. This composite approach, where specific modified components are integrated into the overall microRNA structure, improves both stability and cellular uptake while preserving therapeutic efficacy

Inventive Principle:
Principle #40Composite materials

2Reliability

If microRNA is used for therapeutic treatment of nervous system dysfunction, then therapeutic potential is improved, but cellular uptake is insufficient

Engineering Contradiction:
Improvetherapeutic potentialVSAvoidcellular uptake
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent modifies cellular uptake parameters by introducing deoxyribonucleotides at specific positions of the microRNA structure. This parameter change enhances the ability of microRNA to be taken up by cells while maintaining its therapeutic function, directly addressing the contradiction between therapeutic potential and cellular uptake efficiency

Inventive Principle:
Principle #35Parameter changes

3Stability of the object's composition

If deoxyribonucleotide modifications are added to microRNA, then stability and cellular uptake are improved, but manufacturing complexity increases

Engineering Contradiction:
Improvebiological stabilityVSAvoidmanufacturing complexity
Core Design Contradiction:
Stability of the object's compositionVSEase of manufacture

Solution Approach 1:

The patent applies local quality by making targeted deoxyribonucleotide modifications at specific positions (5' end of guide strand, 3' end of passenger strand) rather than throughout the entire microRNA structure. This localized modification approach improves stability while minimizing manufacturing complexity compared to comprehensive modification

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent uses partial action by modifying only specific positions of the microRNA with deoxyribonucleotides rather than the entire structure. This partial modification achieves the necessary stability improvement while keeping manufacturing processes more manageable than complete modification would require

Inventive Principle:
Principle #16Partial or excessive action

Data Source

PatentUS20240229031A9Microrna compositions and methods of use thereof for the treatment of nervous system dysfunction
Publication Date: 2024.07.11 RUTGERS THE STATE UNIV

AI summary

MicroRNAs, or mimics thereof, for treating a subject suffering from nervous system dysfunction are described. Pharmaceutical compositions, viral vectors or viral particles, and nanoparticles comprising these microRNAs, or mimics thereof, are described. Methods of using these microRNAs, or mimics thereof, pharmaceutical compositions comprising the microRNAs, viral vectors, or nanoparticles are also described herein. These compositions and methods of use will provide novel therapies for patients suffering nervous system dysfunction, including but not limited to alpha-synucleinopathies and SCI.