MLH3-Targeting dsRNA Oligonucleotides for Neurodegenerative Disease Therapy

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

There is a need for efficient and potent methods to silence MLH3 mRNA expression, which is implicated in neurodegenerative diseases such as Huntington's and Alzheimer's, as mutations affecting MLH3 protein function can influence the onset and progression of these conditions.

Innovation Solution

The development of RNA molecules, specifically double-stranded RNA (dsRNA) with sequences complementary to MLH3 nucleic acid sequences, which can inhibit MLH3 gene expression by targeting and degrading MLH3 mRNA, thereby reducing its protein levels in cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional methods are used to silence MLH3 mRNA expression, then the ability to treat neurodegenerative diseases is limited, but the complexity and inefficiency of current approaches remain unresolved

Engineering Contradiction:

Improveefficacy of MLH3 silencingVSAvoidcomplexity of silencing method

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The invention divides the silencing strategy into specific RNA molecule components with defined lengths (8-80 nucleotides) and structural configurations, breaking down the complex problem of gene silencing into manageable, optimized segments that can be systematically designed and deployed

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent systematically varies key parameters including RNA molecule length (8-80 nucleotides), sequence composition (complementary to MLH3 nucleic acid sequences), and structural configuration to optimize silencing efficacy while maintaining manageable complexity

Inventive Principle:

Principle #35Parameter changes

2Productivity

If RNA molecules are designed to be highly complementary to MLH3 sequences for potent silencing, then silencing efficiency improves, but the risk of off-target effects and immunogenicity increases

Engineering Contradiction:

Improvesilencing efficiencyVSAvoidoff-target effects and immunogenicity

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The invention applies local quality by designing RNA molecules with specific sequence characteristics in different regions - highly complementary sequences for target binding while incorporating modifications in other regions to reduce immunogenicity and off-target effects

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent converts the potential harm of high complementarity (immunogenicity and off-target effects) into benefit by using carefully designed complementary sequences that maintain silencing efficiency while minimizing adverse effects through strategic sequence selection and modification

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

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 use of dsRNA molecules effectively inhibits MLH3 gene expression, potentially delaying the onset or managing neurodegenerative diseases by reducing MLH3 protein levels, providing a therapeutic approach for conditions like Huntington's disease.

Implementation Method 1

double-stranded RNA (dsRNA) with sequences complementary to MLH3 nucleic acid sequences, which can inhibit MLH3 gene expression by targeting and degrading MLH3 mRNA

Methodology Applied

Scientific EffectComplementary base pairing:

Implementation Method 2

inhibit MLH3 gene expression by targeting and degrading MLH3 mRNA, thereby reducing its protein levels in cells

Methodology Applied

Scientific EffectRNA interference:

Data Source

PatentUS20230313198A1Oligonucleotides for MLH3 modulation

Publication Date: 2023.10.05 UNIV OF MASSACHUSETTS

AI summary

This disclosure relates to novel MLH3 targeting sequences. Novel MLH3 targeting oligonucleotides for the treatment of neurodegenerative diseases are also provided.