Chimeric Polypeptide Light-Induced Oligomerization for Disease Modeling
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for inducing neurodegenerative disease pathologies in cell lines and animal models require genetic mutations or gross overexpression of proteins, which do not accurately mimic patient pathology, and there is a need for more effective methods to study and potentially treat neurodegenerative diseases such as Alzheimer's, Parkinson's, and ALS.
Innovation Solution
Development of nucleotide sequences encoding chimeric polypeptides with light-induced oligomerization domains and low complexity domains from neurodegenerative disease target proteins, expressed via vectors and induced to oligomerize with blue light, allowing for the recreation of disease pathologies without genetic mutations or overexpression.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If genetic mutations or gross overexpression of proteins are used to induce neurodegenerative disease pathologies, then disease pathologies can be induced in cell lines and animal models, but the models do not accurately mimic patient pathology
Solution Approach 1:
The patent replaces genetic manipulation methods (mutations, overexpression) with optogenetic induction using light-activated proteins. The light-induced oligomerization domain responds to blue light stimulation to trigger protein aggregation, substituting the need for complex genetic engineering with a simpler optical activation system that more accurately recapitulates patient pathology.
Solution Approach 2:
The patent changes the induction parameter from genetic modification to optical stimulation. By using light activation, the system can control the timing, location, and intensity of protein aggregation, providing precise parameter control that improves model accuracy without requiring complex genetic alterations.
2Reliability
If light-induced oligomerization domains are used to induce protein aggregation, then disease pathologies can be accurately mimicked without genetic mutations, but the method requires introduction of expression vectors and specific protein constructs
Solution Approach 1:
The patent segments the protein construct into functional domains: a light-induced oligomerization domain (such as CRY2, CRY1, or LOV) and a low complexity domain from the disease target protein. This segmentation allows independent optimization of each domain's function while maintaining overall simplicity in the construct design.
Solution Approach 2:
The light-induced oligomerization domain serves multiple functions: it acts as a light sensor, an oligomerization trigger, and a control mechanism for protein aggregation. This multi-functionality reduces the need for separate components, simplifying the overall construct despite the added complexity of the fusion protein.
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
This approach enables the induction of neurodegenerative disease pathologies in cells and animals, facilitating the study and potential treatment of diseases like Alzheimer's, Parkinson's, and ALS by recreating protein aggregation and mislocalization, providing a more accurate model of human pathology.
Implementation Method 1
The first nucleotide sequence encodes a light-induced oligomerization domain that undergoes photodimerization upon blue light stimulation
Data Source
AI summary
The present disclosure relates to compounds, compositions, and methods for inducing and analyzing neurodegenerative disease pathologies.