Aggregator Molecules for Targeted Protein Aggregation
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Solution Overview
Problem
Current methods for addressing protein aggregation in biotechnological and medical sciences are limited in their ability to specifically target and control protein function, leading to issues in protein production, immunogenicity, and the management of diseases associated with protein misfolding, such as Alzheimer's and Parkinson's.
Innovation Solution
Development of de novo designed aggregator molecules with beta-aggregation regions fused to binding regions that specifically interact with target proteins, inducing controlled protein aggregation to knock down or knock out the target protein's function.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If protein aggregation is studied as an unwanted phenomenon to be prevented, then disease treatment approaches are limited, but the ability to specifically target and control protein function is insufficient
Solution Approach 1:
The invention converts the harmful phenomenon of protein aggregation into a beneficial tool for protein function control. By designing aggregator molecules that specifically induce aggregation of target proteins, the patent transforms aggregation from a disease-causing mechanism into a precise therapeutic intervention method, allowing selective inactivation of pathological proteins while sparing normal proteins.
Solution Approach 2:
The invention introduces aggregator molecules as intermediary agents that mediate between the researcher/therapist and the target protein. These molecules serve as controllable intermediaries that can be designed with specific binding regions to recognize target proteins and aggregation regions to induce controlled aggregation, providing a bridge for precise protein function modulation.
2Adaptability or versatility
If de novo designed aggregator molecules are used to induce specific protein aggregation, then protein function can be precisely regulated, but the molecular design complexity increases
Solution Approach 1:
The aggregator molecule is segmented into distinct functional modules: a binding region (such as an antibody fragment or peptide) that recognizes the target protein, and one or more aggregation regions (beta-aggregation sequences) that drive aggregate formation. This modular segmentation allows independent optimization of each function and simplifies the design process by treating the molecule as an assembly of standardized functional units.
Solution Approach 2:
The invention creates composite molecules by fusing different functional elements - specifically combining a binding region (from immunoglobulins or peptides) with aggregation-prone sequences (such as amyloidogenic regions). This composite structure integrates the specificity of the binding region with the aggregation capability of the fused sequence, achieving both targeted recognition and controlled aggregation in a single molecule.
3Manufacturing precision
If aggregation regions are fused to binding regions in aggregator molecules, then specific co-aggregation occurs, but the immunogenicity of therapeutic proteins may increase
Solution Approach 1:
The aggregation regions are strategically positioned at specific locations within the aggregator molecule structure, separate from the binding interface. This local placement ensures that aggregation occurs at designated sites while the binding region maintains its native structure and specificity, preventing unwanted immunogenic responses at the protein-protein interaction interface.
Solution Approach 2:
The invention uses naturally occurring aggregation-prone sequences (such as amyloidogenic regions from disease-associated proteins) as templates for the aggregation regions in the aggregator molecules. By copying these naturally evolved sequences, the design leverages their proven aggregation capability while maintaining biocompatibility and reducing the risk of inducing novel immunogenic responses.
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 allows for precise regulation of protein function, offering therapeutic, diagnostic, and research applications by effectively reducing the biological activity of specific proteins, thereby addressing the challenges of protein aggregation and misfolding diseases.
Implementation Method 1
cross beta mediated aggregation is the most frequently occurring and biologically relevant mechanism of aggregation
Implementation Method 2
the composition and the primary structure of a polypeptide determine to a large extent its propensity to aggregate and that small changes may have a huge impact on solubility
Data Source
AI summary
The present invention belongs to the field of protein aggregation. The invention discloses a method for interfering with the function of a target protein and uses a non-naturally, user-designed molecule, designated as aggregator, that has a specificity for a target protein and which induces aggregation upon contact with said target protein. The present invention also discloses such aggregator molecules and their use in therapeutic and diagnostic applications.