XNA Aptamer Particle Display for Enzymatic Stability
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Solution Overview
Problem
Existing aptamers are prone to digestion by enzymes, making them unsuitable for in vivo applications, and most are limited in their target specificity and stability.
Innovation Solution
The development of an XNA aptamer particle display format that uses artificial genetic polymers (xeno-nucleic acids or XNAs) to create a library of monoclonal XNA aptamer particles (mXNAPs) for rapid screening of aptamers with high affinity and specificity to desired targets.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional aptamers are used, then they can bind to targets with high affinity, but they are susceptible to digestion by enzymes and lack stability for in vivo applications
Solution Approach 1:
The patent changes the chemical parameter of the nucleic acid backbone from natural DNA/RNA to artificial XNA structures (such as TNA, HNA, CeNA, FANA, LNA). This parameter change fundamentally alters the chemical properties of the aptamer, making it resistant to enzymatic digestion while maintaining or enhancing target binding affinity and stability for in vivo applications
Solution Approach 2:
The patent creates composite structures by combining artificial XNA aptamers with particle display technology. This composite approach allows the XNA aptamers to be displayed on particle surfaces, enabling both high stability from the XNA backbone and high affinity binding to diverse targets through the aptamer sequences
2Productivity
If in vitro selection is performed to generate aptamers, then high target binding affinity can be achieved, but the process is time-consuming and requires multiple rounds of selection
Solution Approach 1:
The patent performs preliminary actions by pre-synthesizing and displaying diverse XNA aptamer sequences on particle surfaces before exposure to the target. This pre-prepared library allows for rapid screening without requiring multiple iterative rounds of in vitro selection, significantly reducing the time needed to identify high-affinity binders
Solution Approach 2:
The patent uses particle display technology where each particle serves as a copy bearing multiple identical XNA aptamer sequences. This copying approach allows parallel screening of numerous aptamer variants simultaneously, dramatically increasing productivity compared to traditional sequential selection methods
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 method enables the identification of biologically stable XNA aptamers that maintain high target binding affinity and specificity, overcoming the limitations of traditional aptamers in terms of stability and target range.
Implementation Method 1
extending the 3′ end of the self-priming stem-loop in the presence of a polymerase capable of synthesizing an XNA from a DNA template and one or more XNA triphosphate molecules (xNTPs)
Implementation Method 2
contacting the double stranded XNA-DNA display templates with a primer which anneals to the loop region of the stem-loop structure
Implementation Method 3
extending the DNA primer using dNTPs and a DNA polymerase to displace the XNA portion of the XNA-DNA display templates
Data Source
AI summary
The invention provides xeno-nucleic acid particle display libraries, methods for identifying functional non-natural nucleic acid (XNA) aptamers using the particle display libraries, and compositions comprising XNA aptamers identified by screening candidate molecules using the xeno-nucleic acid particle display libraries.