ALS Gene Discovery via Targeted RNA-Binding Protein Screening

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Solution Overview

Problem

Current approaches are inadequate for identifying genetic markers for amyotrophic lateral sclerosis (ALS) and developing therapeutic targets, particularly due to the high cost and time-consuming nature of genome sequencing and the need for innovative methods to elucidate causality in neurodegenerative diseases like ALS.

Innovation Solution

A yeast functional screen identifies RNA-binding proteins with properties similar to TDP-43 and FUS, such as EWSR1 and TAF15, and their associated mutations, which are used to develop diagnostic assays and screening methods for predicting ALS risk and identifying therapeutic agents that inhibit TDP-43 associated complex formation with these proteins.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If complete genome sequencing is performed to discover rare pathogenic mutations, then disease gene discovery capability is improved, but cost and time consumption increase significantly

Engineering Contradiction:

Improvedisease gene discovery capabilityVSAvoidtime consumption

Core Design Contradiction:

Measurement precisionVSLoss of time

Solution Approach 1:

The patent extracts and focuses on specific RNA-binding protein genes (EWSR1, TAF15) and their mutations that are directly associated with ALS pathogenesis, rather than performing complete genome sequencing. This targeted approach isolates the most relevant genetic markers for ALS risk prediction, significantly reducing time and cost while maintaining diagnostic precision

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent segments the complex task of ALS gene discovery into specific focus areas: identifying mutations in RNA-binding proteins EWSR1 and TAF15. By dividing the genome analysis into targeted segments related to RNA metabolism defects, the methodology achieves efficient disease gene discovery without requiring comprehensive genome sequencing

Inventive Principle:

Principle #1Segmentation

2Measurement precision

If targeted mutation analysis of EWSR1 and TAF15 is performed, then ALS risk prediction accuracy is improved, but diagnostic complexity is reduced

Engineering Contradiction:

ImproveALS risk prediction accuracyVSAvoiddiagnostic complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent extracts specific mutations in EWSR1 (exon 16: 1532 G>C, exon 17: 1655 C>T) and TAF15 (exon 14: 1172 G>A, exon 15: 1222 C>T) as diagnostic markers for ALS. This extraction of key genetic markers simplifies the diagnostic process while maintaining high prediction accuracy for ALS risk assessment

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the diagnostic parameters from comprehensive genome-wide analysis to specific mutation detection in EWSR1 and TAF15 genes. By shifting focus to these specific genetic parameters with known ALS associations, the methodology achieves accurate risk prediction with simplified testing protocols

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS8969005B2Gene targets associated with amyotrophic lateral sclerosis and methods of use thereof

Publication Date: 2015.03.03 THE TRUSTEES OF THE UNIV OF PENNSYLVANIA

AI summary

Compositions and methods for diagnosis and treatment of ALS are provided.