DNA Aptamers Inhibit Alpha-Synuclein Aggregation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current therapeutic strategies for neurodegenerative diseases associated with alpha-synuclein, such as Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, are inadequate in preventing or reversing the aggregation of alpha-synuclein protein, which is a key pathological feature of these conditions.
Innovation Solution
Development of DNA aptamers that specifically bind to alpha-synuclein protein, preventing its aggregation by forming complexes and promoting the formation of larger aggregates, which are then recovered and amplified, and used in liposomes with targeting moieties for delivery to treat neurodegenerative diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapeutic strategies are used, then treatment of neurodegenerative diseases is provided, but prevention or reversal of alpha-synuclein aggregation is inadequate
Solution Approach 1:
The patent uses DNA aptamers as intermediary molecules that specifically bind to alpha-synuclein protein. These aptamers act as mediators between the therapeutic agent and the target protein, forming stable complexes that prevent aggregation. The aptamers serve as a bridge that enables selective recognition and binding of alpha-synuclein, thereby preventing its aggregation into harmful aggregates while providing a targeted therapeutic approach.
Solution Approach 2:
The patent employs aptamers with specific nucleic acid sequences that have been optimized to bind alpha-synuclein with high affinity. By changing the chemical and structural parameters of the binding molecule (using nucleic acid-based aptamers instead of traditional small molecules or proteins), the therapy achieves reliable prevention of aggregation. The aptamers' structural characteristics enable them to effectively interfere with the aggregation process.
2Object-generated harmful factors
If aptamers are used to bind alpha-synuclein, then aggregation is prevented, but device complexity increases due to aptamer selection and production processes
Solution Approach 1:
The patent utilizes the SELEX (Systematic Evolution of Ligands by EXponential enrichment) method, which is a self-organizing selection process. The large library of random nucleic acid sequences automatically undergoes iterative selection and amplification cycles, where sequences that bind alpha-synuclein are enriched through natural selection principles. This self-service approach allows the system to identify and produce effective aptamers without requiring complex manual intervention at each step, thereby managing the production complexity through automated, self-directed processes.
Solution Approach 2:
The patent performs preliminary actions by first creating a diverse library of nucleic acid sequences and pre-selecting those with binding capability through the SELEX process before actual therapeutic application. The aptamers are pre-produced and characterized in vitro to ensure their effectiveness against alpha-synuclein aggregation. This preliminary preparation and selection work is done in advance, allowing the therapeutic agent to be ready for deployment without requiring complex on-demand production.
3Object-generated harmful factors
If aptamers are administered to treat neurodegenerative diseases, then alpha-synuclein-positive cells are reduced, but delivery efficiency must be optimized
Solution Approach 1:
The patent employs liposomes as intermediary delivery vehicles that carry the aptamers to the target sites in the brain. These liposomal carriers act as mediators between the aptamer therapeutic agent and the alpha-synuclein-positive cells. The liposomes protect the aptamers during transport, enable their delivery across biological barriers, and facilitate their accumulation at the target site, thereby optimizing delivery efficiency and enabling effective reduction of alpha-synuclein-positive cells.
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 aptamers effectively inhibit alpha-synuclein fibrilization, reducing the number of alpha-synuclein-positive cells in the brain, thereby providing a potential therapeutic approach to manage neurodegenerative diseases by targeting and reducing protein aggregation.
Implementation Method 1
an aptamer that binds to alpha-synuclein protein, comprising: a nucleic acid comprising or consisting of any one of α-syn-1(SEQ ID NO: 1), α-syn-2(SEQ ID NO: 2), α-syn-3(SEQ ID NO: 3), α-syn-4(SEQ ID NO: 4), or α-syn-5(SEQ ID NO: 5)
Implementation Method 2
a nucleic acid that hybridizes with the complementary strand of the nucleic acid of a)
Implementation Method 3
said recovery step comprises an ultracentrifugation step
Implementation Method 4
an amplification step of recovering the single-stranded nucleic acid from the complex and then amplifying the single-stranded nucleic acid by a nucleic acid amplification method
Implementation Method 5
a liposome comprising, one or more lipids, and at least one aptamer of any one of claims 1 to 3
Data Source
AI summary
The present disclosure relates generally to the selection of DNA aptamers that prevent aggregation, or fibrilization of alpha-synuclein protein. The aptamers described herein are of use as a therapeutic tool to prevent protein aggregation in neurodegenerative disease.