BK Virus Detection via Conserved Region Primers

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Solution Overview

Problem

Current diagnostic tests for BK virus lack sensitivity for detecting low titers and fail to differentiate between BK virus and other polyoma viruses like JC virus, leading to issues with false positives and false negatives, particularly in immunocompromised patients and renal transplant recipients.

Innovation Solution

The development of nucleic acid-based methods and kits that target conserved regions of the BK virus genome, using specific primer pairs and probes for real-time PCR, allowing for sensitive and specific detection of BK virus while avoiding detection of closely related viruses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If existing diagnostic tests are used to detect polyomaviruses, then virus detection is possible, but sensitivity for detecting low titers is insufficient

Engineering Contradiction:
Improvedetection sensitivityVSAvoidfalse negative rate
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent modifies detection parameters by targeting specific conserved genomic regions (control region and early region) with optimized primer pairs and probe sequences. This allows the assay to detect low viral titers effectively by changing the detection target from general polyomavirus sequences to specific BK virus regions with known conservation patterns across different strains.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent replaces conventional viral culture or indirect detection methods with direct nucleic acid detection using real-time PCR. This substitution enables sensitive detection of viral DNA even at low titers, eliminating the need for viral isolation and reducing false negatives associated with culture-based methods.

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

2Measurement precision

If existing diagnostic tests are used to detect polyomaviruses, then virus detection is possible, but specificity to differentiate BK virus from other polyoma viruses is insufficient

Engineering Contradiction:
Improvedetection specificityVSAvoidfalse positive rate
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent applies local quality by designing primers and probes that target specific conserved regions unique to BK virus (control region and early region) rather than using general polyomavirus sequences. This localized targeting ensures the assay specifically detects BK virus while avoiding cross-reaction with JC virus or other polyomaviruses, thereby reducing false positives.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent segments the detection strategy by using multiple specific primer pairs targeting different conserved regions (control region and early region) of BK virus. This segmentation allows the assay to maintain high specificity through region-specific priming while ensuring comprehensive detection across different viral strains and genotypes.

Inventive Principle:
Principle #1Segmentation

3Measurement precision

If detection assays target variable regions of BK virus genome, then detection of specific strains is possible, but detection of different BK virus genotypes becomes unreliable

Engineering Contradiction:
Improvestrain detection capabilityVSAvoidgenotype detection coverage
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent changes the detection approach by targeting conserved regions (control region and early region) that maintain sequence conservation across different BK virus genotypes and strains. This parameter change from variable to conserved regions ensures the assay reliably detects all BK virus genotypes while still providing strain-specific information through sequence analysis of the amplified products.

Inventive Principle:
Principle #35Parameter changes

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

These methods provide rapid, reliable, and specific detection of BK virus, reducing false positives and negatives, and are suitable for both diagnostic and therapeutic monitoring in clinical settings.

Implementation Method 1

The invention provides methods and compositions for rapid, sensitive, and highly specific nucleic acid-based (e.g., DNA based) detection of a BK virus in a sample. The methods involve detecting a target nucleic acid having a target sequence of conserved regions of BK viral genome.

Methodology Applied
Scientific EffectPolymerase chain reaction:

Implementation Method 2

The invention features primer pairs and kits, for use in the methods of the invention.

Methodology Applied
Scientific EffectNucleic acid hybridization:

Data Source

PatentEP1910578B1Methods and compositions for detecting BK virus
Publication Date: 2015.06.10 QUEST DIAGNOSTICS INFECTIOUS DISEASE INC
  • EP1910578B1 patent drawingFigure 1A
  • EP1910578B1 patent drawingFigure 1B
  • EP1910578B1 patent drawingFigure 1C

AI summary

The invention provides methods and compositions for rapid, sensitive, and highly specific nucleic acid-based (e.g., DNA based) detection of a BK virus in a sample. In general, the methods involve detecting a target nucleic acid having a target sequence of a conserved region of BK viral genomes. The invention also features compositions, including primers, probes, and kits, for use in the methods of the invention.