Oligonucleotide Probes for HBV Pre-S Deletion Detection

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Solution Overview

Problem

Current methods lack a rapid and accurate means to detect deletion mutations in the Pre-S region of the Hepatitis B virus (HBV) genome, which are associated with an increased risk of cirrhosis and hepatocellular carcinoma (HCC).

Innovation Solution

Development of novel oligonucleotide combinations (A, B, and C) that target specific sequences in the HBV Pre-S region, allowing for the detection of deletions through hybridization with a DNA chip, enabling assessment of a patient's risk of developing cirrhosis or HCC.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional detection methods are used for HBV Pre-S region deletions, then the detection process is simple, but the detection speed and accuracy are insufficient

Engineering Contradiction:
Improvedetection accuracyVSAvoiddetection system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention divides the Pre-S region detection into multiple specific oligonucleotide probes targeting different segments (Pre-S1 and Pre-S2 regions). Each probe set is designed to detect specific deletion patterns, allowing comprehensive coverage of potential deletion sites through segmented detection rather than a single comprehensive method

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention introduces oligonucleotide probes as intermediary molecules that hybridize specifically to complementary sequences in the HBV Pre-S region. These probes act as mediators between the target DNA and the detection system, enabling indirect but highly specific detection of deletion mutations through hybridization patterns

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If comprehensive deletion detection is performed across the entire Pre-S region, then detection accuracy improves, but detection time increases

Engineering Contradiction:
Improvedetection accuracyVSAvoiddetection time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The invention performs preliminary action by pre-designing and preparing multiple specific oligonucleotide probes that target known deletion-prone regions within the Pre-S sequence. These probes are prepared in advance and can be simultaneously applied to the sample, allowing rapid parallel detection of multiple potential deletion sites without sequential analysis

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The invention transitions from linear sequential detection to parallel multi-dimensional detection by using multiple oligonucleotide probes that can simultaneously hybridize to different regions of the Pre-S sequence. This dimensional change allows comprehensive coverage of the entire Pre-S region through concurrent detection rather than sequential scanning

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

3Adaptability or versatility

If multiple oligonucleotide probes are used to cover all deletion sites, then detection comprehensiveness improves, but the complexity of probe design and selection increases

Engineering Contradiction:
Improvedetection coverageVSAvoidprobe combination complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The invention creates universal probe sets that can detect multiple types of deletions simultaneously. The oligonucleotide probes are designed with universal characteristics that allow them to function across different genotype variations while maintaining specificity for deletion detection, reducing the need for genotype-specific probe designs

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

Solution Approach 2:

The invention systematically varies key parameters of the oligonucleotide probes including length (20-50 nucleotides), melting temperature, and sequence composition to optimize detection sensitivity and specificity. By adjusting these parameters, the probe sets achieve comprehensive deletion coverage while maintaining manageable complexity through standardized design criteria

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

The oligonucleotide combinations provide a rapid and accurate method for identifying deletions in the HBV Pre-S region, effectively assessing the risk of cirrhosis and HCC in HBV carriers by distinguishing between wild-type and deleted sequences.

Implementation Method 1

a test HBV DNA is hybridized with oligonucleotide combination (A) and the results thus obtained are compared with the results obtained from hybridizing the same oligonucleotide combination with wild-type HBV DNA

Methodology Applied
Scientific EffectHybridization:

Data Source

PatentUS8293474B2Oligonucleotides and use thereof for determining deletion in HBV Pre-S region
Publication Date: 2012.10.23 NATIONAL HEALTH RESEARCH INSTITUTE
  • US8293474B2 patent drawing
  • US8293474B2 patent drawing
  • US8293474B2 patent drawing

AI summary

This invention provides combinations of novel oligonucleotides and their use in detecting a deletion(s) in the Pre-S region of HBV. Such a deletion(s) is associated with an increased risk of developing cirrhosis or hepatocellular carcinoma.