Universal HIV Detection Probe Design for Variant Sensitivity

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Solution Overview

Problem

Current methods for detecting HIV genetic variants face challenges in achieving high sensitivity and specificity, often requiring multiple probes which can lower assay sensitivity and make it difficult to detect a wide range of variants effectively.

Innovation Solution

The use of specific nucleic acid molecules with universal nucleotides and cytidine analogs with C-5 modifications, along with designed primers and probes, allows for the amplification and detection of HIV in a sample, enabling the detection of multiple genetic variants with improved sensitivity and specificity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If multiple probes with different specificity are designed to detect various HIV genetic variants, then the ability to detect a wide range of variants (specificity) is improved, but the assay sensitivity is lowered

Engineering Contradiction:
Improveability to detect genetic variantsVSAvoidassay sensitivity
Core Design Contradiction:
Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The patent applies universality by designing a single probe sequence (SEQ ID NO: 6) that can detect multiple HIV genetic variants including different subtypes and circulating recombinant forms. This universal probe replaces the need for multiple variant-specific probes, thereby maintaining high assay sensitivity while detecting a broad range of HIV genetic diversity.

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

Solution Approach 2:

The patent utilizes parameter changes by modifying the probe sequence design to incorporate regions of high conservation across HIV variants. By changing the targeting parameter from variant-specific regions to conserved regions, the probe maintains binding capability across diverse genetic variants without sacrificing sensitivity.

Inventive Principle:
Principle #35Parameter changes

2Adaptability or versatility

If probes are designed from conserved genomic regions to detect multiple variants, then the assay can detect a wide range of genetic variants (specificity), but the sensitivity may be reduced compared to variant-specific probes

Engineering Contradiction:
Improvedetection of genetic variantsVSAvoidassay sensitivity
Core Design Contradiction:
Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The probe is designed to be universal by targeting conserved genomic regions that are present across all HIV variants. This allows a single probe to perform the function of multiple variant-specific probes while maintaining sensitivity through optimized binding to the conserved region.

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

Solution Approach 2:

The patent segments the HIV genome analysis by focusing on specific conserved regions that can be targeted by a single probe. Rather than attempting to detect all variants simultaneously with multiple probes, the methodology segments the detection task into targeting a specific conserved segment that represents all variants.

Inventive Principle:
Principle #1Segmentation

3Reliability

If multiple probes are used to ensure detection of all HIV variants, then pathogen safety is improved, but the complexity of the assay increases

Engineering Contradiction:
Improvepathogen safetyVSAvoidassay complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent reduces assay complexity by replacing multiple probes with a single universal probe that maintains pathogen safety. The universal probe achieves the same reliability as multiple probes by targeting conserved regions essential for HIV function, which are present in all variants.

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

Solution Approach 2:

The methodology merges the function of multiple variant-specific probes into a single universal probe. By combining the detection capability for all HIV variants into one probe targeting a conserved region, the assay complexity is reduced while maintaining comprehensive detection.

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

This approach enhances the ability to detect HIV across various genetic variants, improving pathogen safety and cost-effectiveness by increasing the sensitivity and specificity of the detection process.

Implementation Method 1

contacting an amplicon generated by the forward and the reverse primer with a first oligonucleotide comprising the sequence as set forth in SEQ ID NO: 10 and a second oligonucleotide comprising the sequence as set forth in SEQ ID NO: 11, wherein detection of the amplicon is indicative of the presence of the HIV in the sample

Methodology Applied
Scientific EffectHybridization:

Data Source

PatentEP2643460B1Methods, compositions, and kits for determining human immunodeficiency virus (HIV)
Publication Date: 2017.07.26 GRIFOLS THERAPEUTICS INC

AI summary

The present invention relates to compositons, methods, and kits for determining the presence or absence of HIV in a sample, in particular for deiennining HI V- 1 group M, HlV- 1 group O, and/or HIV-2, in particular for simultaneous determining of HIV- 1 group M, HIV- 1 group O, and H IV-2.