Thrombin-Binding Circular Aptamer for Nuclease Resistance
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Aptamers are susceptible to degradation by nucleases in biological systems, limiting their half-life and practical application in biomedical fields, and chemically modified aptamers have poor biocompatibility.
Innovation Solution
Development of a thrombin binding circular aptamer (TBCA) with specific nucleotide sequences and chemical modifications to enhance biostability and biocompatibility, including nucleotide substitutions, deletions, additions, and chemical group modifications, resulting in a half-life of up to 8 hours in 50% serum.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If chemical drugs are used to target thrombin, then therapeutic efficacy is achieved, but toxic side effects occur due to poor biocompatibility
Solution Approach 1:
The patent changes the chemical parameters of the therapeutic agent by using nucleic acid-based aptamers instead of traditional chemical drugs. This fundamental parameter change allows for specific thrombin binding through sequence complementarity while avoiding the toxic side effects associated with chemical drugs, as the aptamers are biocompatible nucleic acid molecules.
2Reliability
If monoclonal antibody drugs are prepared, then specific thrombin binding is achieved, but production costs increase and batch consistency deteriorates
Solution Approach 1:
The patent replaces the biological production system (organism-dependent monoclonal antibody production) with an in vitro chemical synthesis system. The aptamers are synthesized chemically rather than produced through living organisms, which eliminates the high costs and batch-to-batch variability associated with biological production while maintaining specific thrombin binding capability.
3Object-affected harmful factors
If unmodified aptamers are used, then biocompatibility is maintained, but half-life in blood decreases due to nuclease degradation
Solution Approach 1:
The patent creates a composite structure by combining the aptamer sequence with a circular backbone structure. This composite design integrates the thrombin-binding functionality of the aptamer with the enhanced stability of the circular configuration, achieving both biocompatibility and extended half-life by protecting against nuclease degradation while maintaining the biocompatible nucleic acid nature.
4Duration of action of moving object
If chemical modifications are applied to aptamers, then resistance to nuclease degradation improves, but biocompatibility deteriorates
Solution Approach 1:
The patent changes the structural parameter of the aptamer from linear to circular configuration. This parameter change inherently provides resistance to nuclease degradation without requiring additional chemical modifications that would compromise biocompatibility. The circular structure itself serves as the protective mechanism, maintaining the natural biocompatible properties of nucleic acids.
Data Source
AI summary
Provided is a thrombin binding circular aptamer, the nucleotide sequence thereof being at least one selected from a) to e): a) a nucleotide sequence in SEQ ID NO:1, wherein the 5′ end and 3′ end are connected to form a ring; b) a nucleotide sequence obtained by substitution in the nucleotide sequence in SEQ ID NO:1, the obtained nucleotide sequence being a circular DNA molecule capable of specific recognition of thrombin; c) a nucleotide sequence obtained by deletion in the nucleotide sequence in SEQ ID NO:1, the obtained nucleotide sequence being a circular DNA molecule capable of specific recognition of thrombin; d) a nucleotide sequence obtained by adding one or more nucleotides to the nucleotide sequence in SEQ ID NO:1; and e) a nucleotide sequence obtained by modification of the nucleotide sequence in SEQ ID NO:1 with a chemical group.