VEGF-Binding Nucleic Acids That Preserve Protein Function
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Solution Overview
Problem
Existing nucleic acid molecules that bind to targets inhibit the function of the target protein, such as vascular endothelial growth factor (VEGF), which is undesirable.
Innovation Solution
A method for producing nucleic acid molecules that bind to VEGF without inhibiting its function, involving the selection of nucleic acid molecules that specifically interact with VEGF through SELEX (Systematic Evolution of Ligands by Exponential Enrichment) and identifying polynucleotides with specific base sequences or high sequence identity, forming defined secondary structures.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If nucleic acid molecules are designed to bind to target proteins, then binding capability is improved, but the function of the target protein is inhibited
Solution Approach 1:
The invention applies local quality by designing the nucleic acid molecule to bind to a specific local region (heparin-binding domain) of the VEGF protein rather than the entire protein structure. This localized binding to the HBD region allows the nucleic acid to interact with VEGF without blocking the receptor-binding interface, thus maintaining VEGF's biological function while achieving specific binding
Solution Approach 2:
The invention uses an intermediary approach by introducing a nucleic acid molecule as a mediator that binds to VEGF's heparin-binding domain. This intermediary binding provides detection or regulatory capability without directly interfering with the VEGF-receptor interaction, allowing the target protein to maintain its natural function
Data Source
AI summary
The present invention provides a method for producing a nucleic acid molecule that can obtain a nucleic acid molecule that binds to a target and does not inhibit a function of the target. The production method for a nucleic acid molecule of the present invention is a method for producing a nucleic acid molecule that binds to a first biological molecule and does not inhibit a function of the first biological molecule, the method including the steps of:(A) bringing a candidate nucleic acid molecule into contact with the first biological molecule to select a nucleic acid molecule that has bound to the first biological molecule as a first selected nucleic acid molecule; and(B) selecting the first selected nucleic acid molecule as an intended nucleic acid molecule.