Viral Detection via Universal Primers and Mass Spectrometry

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Solution Overview

Problem

Current methods for detecting adventitious viral contaminants in cell cultures and biologicals are not specific, do not provide information on the source of reverse transcriptase activity, and are not practical for high-throughput, quality-controlled detection of a broad range of viral agents, including unknown or uncharacterized viruses.

Innovation Solution

The use of oligonucleotide primers and kits that hybridize to conserved sequence regions of viral nucleic acids, amplifying specific regions to produce molecular mass and base composition signatures for identification and quantification of adventitious viruses using mass spectrometry analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If PCR-based detection methods are used to increase sensitivity and identify particular adventitious agents, then detection sensitivity improves, but the complexity of the testing protocol and time required for analysis increases

Engineering Contradiction:
Improvedetection sensitivityVSAvoidtesting protocol complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent combines multiple detection functions into a single mass spectrometry-based assay. By using universal primers that amplify conserved viral regions followed by mass spectrometric analysis, the method merges sensitivity enhancement, viral identification, and characterization into one integrated protocol, eliminating the need for multiple separate PCR-based tests

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The invention employs universal primers targeting conserved viral sequences that can detect multiple virus families simultaneously. This multi-functional approach allows a single assay to identify diverse adventitious agents including retroviruses, parvoviruses, and other contaminants without requiring virus-specific protocols for each agent

Inventive Principle:
Principle #6Universality (Multi-functionality)

2Reliability

If multiple PCR strategies and co-cultivation assays are used to detect retroviral integration and tumorigenesis risk, then detection comprehensiveness improves, but the time and resources required for complete analysis increase

Engineering Contradiction:
Improvedetection comprehensivenessVSAvoidanalysis time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent performs preliminary amplification of conserved viral regions using universal primers before mass spectrometric analysis. This preliminary action captures potential retroviral sequences early in the workflow, allowing subsequent rapid identification through mass spectrometry without requiring time-consuming follow-up co-cultivation assays or multiple sequential PCRs

Inventive Principle:
Principle #10Preliminary action

3Adaptability or versatility

If broad-range PCR and mass spectrometry analysis are used to detect unknown or uncharacterized viruses, then adaptability to diverse viral agents improves, but the cost of implementation increases

Engineering Contradiction:
Improvedetection rangeVSAvoidimplementation cost
Core Design Contradiction:
Adaptability or versatilityVSEase of manufacture

Solution Approach 1:

The patent replaces traditional sequencing-based viral identification with mass spectrometry. This substitution eliminates the need for expensive, time-consuming Sanger sequencing or next-generation sequencing while maintaining broad detection capability. The mass spectrometric analysis of amplified viral DNA provides rapid, cost-effective identification of unknown viruses through molecular weight fingerprinting

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

Enables rapid, sensitive, and cost-effective detection of adventitious viral agents, including previously unknown viruses, at the species or sub-species level, facilitating the identification and quantification of contaminants in a high-throughput, quality-controlled manner.

Implementation Method 1

contacting nucleic acids from the sample with at least one primer pair, wherein each of the two primers of each of said at least one primer pair hybridizes to a conserved sequence region of a Dependovirus nucleic acid

Methodology Applied
Scientific EffectHybridization:

Implementation Method 2

amplifying the two conserved sequence regions and the variable region to produce an amplification product

Methodology Applied
Scientific EffectPCR amplification:

Implementation Method 3

determining the molecular mass of said amplification product by mass spectrometry

Methodology Applied
Scientific EffectMass spectrometry:

Data Source

PatentEP1957678B1Compositions for use in identification of adventitious contaminant viruses
Publication Date: 2012.06.13 IBIS BIOSCI
  • EP1957678B1 patent drawingFigure 1
  • EP1957678B1 patent drawingFigure 2
  • EP1957678B1 patent drawingFigure 3

AI summary

The present invention provides oligonucleotide primers, compositions, and kits containing the same for rapid identification of viruses by amplification of a segment of viral nucleic acid followed by molecular mass analysis.