EBV Nucleic Acid Detection Using Segmented Oligonucleotide Probes

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Solution Overview

Problem

There is a need for a simplified and accurate approach to detect Epstein-Barr virus (EBV) infection, as existing methods struggle to specifically and sensitively detect EBV without cross-reacting with other herpesvirus or human nucleic acids.

Innovation Solution

A reaction mixture and method are developed that include a detection probe oligomer and a pair of amplification oligomers specific to EBV nucleic acids. The detection probe is up to 30 nucleotides in length and includes the base sequence of SEQ ID NO:22 or its complement, while the amplification oligomers are 18-25 nucleotides in length and include sequences from SEQ ID NO:3 and SEQ ID NO:4. This allows for the specific amplification and detection of EBV nucleic acids in a sample.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional detection methods are used to detect EBV, then detection can be performed, but cross-reactivity with other herpesvirus and human nucleic acids occurs, reducing specificity

Engineering Contradiction:
Improvedetection specificityVSAvoidcross-reactivity
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The detection system is segmented into multiple specific oligonucleotide probes (detection probe and amplification oligomers) that each target specific EBV nucleic acid sequences. This segmentation allows the system to distinguish EBV from other herpesviruses and human nucleic acids, achieving high specificity while avoiding cross-reactivity issues.

Inventive Principle:
Principle #1Segmentation

2Measurement precision

If detection sensitivity is increased to detect low levels of EBV, then more copies can be detected, but the risk of detecting non-EBV nucleic acids increases

Engineering Contradiction:
Improvedetection sensitivityVSAvoiddetection accuracy
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The system uses specific oligonucleotide probes as intermediaries that bind selectively to EBV nucleic acid sequences. The detection probe (SEQ ID NO:22) and amplification oligomers (SEQ ID NO:3 and SEQ ID NO:4) act as mediators that enable sensitive detection of low-copy EBV while maintaining reliability through their sequence-specific binding, preventing false detection of non-EBV nucleic acids.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If complex detection protocols are used to improve accuracy, then detection precision improves, but the complexity of the procedure increases

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

Solution Approach 1:

The detection and amplification functions are merged into a single reaction mixture containing the detection probe and amplification oligomers. This combination allows the system to achieve high detection accuracy through specific sequence recognition while simplifying the procedure by eliminating separate detection and amplification steps.

Inventive Principle:
Principle #5Merging (Combining)

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 described method enables sensitive and specific detection of EBV, distinguishing it from other herpesviruses and human nucleic acids, with the ability to detect as few as 50 copies of EBV per milliliter in a sample within a reasonable time frame.

Implementation Method 1

a detection probe oligomer for detecting EBV nucleic acids

Methodology Applied
Scientific EffectHybridization:

Implementation Method 2

performing an in vitro nucleic acid amplification reaction using the oligomer combination, where any EBV target nucleic acid, if present in the sample, is a template for generating an amplification product

Methodology Applied
Scientific EffectNucleic acid amplification:

Data Source

PatentUS20250146090A1Compositions and Methods for Detecting Nucleic Acids of Epstein-Barr Virus
Publication Date: 2025.05.08 GEN PROBE INC

AI summary

Disclosed are compositions, methods, and kits that can be used to Epstein-Barr virus (EBV) in a sample undergoing testing. Nucleic acids of EBV can be isolated, amplified and detected with specificity, and without interference from non-EBV organisms. In some embodiments, nucleic acids used for amplification are isolated from human blood, or blood products. Nucleic acid isolation, amplification and detection steps can all be carried out using an automated instrument.