DNA Aptamer LTA Detection Resolving RNA Stability Trade-offs

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Solution Overview

Problem

RNA aptamers for detecting lipoteichoic acid (LTA) are less stable and less tolerant of variations in solution chemistry compared to DNA aptamers, limiting their effectiveness in detecting Gram-positive bacteria.

Innovation Solution

Development of DNA aptamers with specific loop and double-stranded stem structures, capable of binding to LTA, which can be labeled with optical or electrochemical labels for detection, and their use in kits for identifying Gram-positive bacteria in medical samples.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If RNA aptamers are used for detecting LTA, then binding affinity can be achieved, but stability and tolerance to solution chemistry variations deteriorate

Engineering Contradiction:
Improvebinding affinityVSAvoidstability
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent changes the chemical composition parameter from RNA to DNA, which fundamentally alters the stability characteristics while maintaining binding capability. DNA aptamers exhibit enhanced chemical stability and resistance to degradation compared to RNA aptamers, directly resolving the stability issue while preserving LTA binding affinity

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a DNA version as a copy of the RNA aptamer sequence, transferring the binding function to a more stable molecular platform. This copying approach allows the aptamer to maintain its target recognition capability while gaining improved stability and tolerance to solution variations

Inventive Principle:
Principle #26Copying

2Reliability

If RNA aptamers are used for detecting LTA, then specific binding can be achieved, but tolerance to solution chemistry variations deteriorates

Engineering Contradiction:
Improvespecific bindingVSAvoidtolerance to solution chemistry variations
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

Changing from RNA to DNA chemistry provides broader adaptability to different solution conditions. DNA aptamers tolerate a wider range of pH levels, salt concentrations, and buffer compositions without losing binding specificity, enabling the assay to function reliably across diverse sample matrices including serum and other biological fluids

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If monoclonal antibodies are used for sandwich immunoassay, then detection sensitivity can be achieved, but assay complexity and cost increase

Engineering Contradiction:
Improvedetection sensitivityVSAvoidassay complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces protein-based antibodies with nucleic acid-based aptamers, creating a functional copy that performs similar binding functions. This substitution simplifies the assay system by eliminating the need for complex antibody production, purification, and validation processes while maintaining detection sensitivity

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The patent substitutes the biological protein-based recognition system (antibodies) with a nucleic acid-based system (aptamers). This substitution enables in vitro synthesis through automated oligonucleotide synthesis, replacing complex biological manufacturing with a more controllable and scalable chemical synthesis process

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

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 DNA aptamers provide stable and specific binding to LTA, enabling effective detection of Gram-positive bacteria in various conditions, improving upon the limitations of RNA aptamers in terms of stability and binding affinity.

Implementation Method 1

DNA aptamers with specific loop and double-stranded stem structures, capable of binding to LTA

Methodology Applied
Scientific EffectMolecular recognition and binding:

Data Source

PatentUS11970698B2Lipoteichoic acid (LTA) aptamers and associated methods
Publication Date: 2024.04.30 FRESENIUS MEDICAL CARE HOLDINGS INC
  • US11970698B2 patent drawing
  • US11970698B2 patent drawing
  • US11970698B2 patent drawing

AI summary

Described are a number of aptamers that are specific to bind with lipoteichoic acid (LTA), and associated methods.