Segmented Nucleic Acid Probes for HPV Detection
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Solution Overview
Problem
Existing nucleic acid hybridization probes for in situ hybridization applications lack improved detectability and specificity, particularly in detecting HPV genes or transcripts in human cervical cell specimens.
Innovation Solution
The development of non-naturally occurring linear nucleic acid molecules with a series of first nucleic acid segments complementary to a preselected target sequence, interspersed with spacer segments that are not complementary to the target sequence and labeled with detectable labels, such as fluorescent moieties or haptens.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If nucleic acid probes are labeled with detectable labels to improve detectability, then the detectability is enhanced, but the sequence specificity may be affected
Solution Approach 1:
The probe is divided into multiple segments: target-complementary segments that maintain sequence specificity and spacer segments that carry detectable labels. This segmentation allows labeling without compromising the hybridization specificity of the target-complementary segments.
Solution Approach 2:
Different parts of the probe have different functions: the target-complementary segments are designed for specific hybridization to the target sequence, while the spacer segments are designed to carry detectable labels. This local differentiation allows each part to optimize its specific function.
2Measurement precision
If detectable labels are added to nucleic acid probes, then detectability is improved, but the complexity of the probe structure increases
Solution Approach 1:
The probe structure is segmented into functional modules (target-complementary segments and spacer segments with labels), making the complexity manageable and the design systematic rather than arbitrary.
Solution Approach 2:
The spacer segments serve multiple functions: they provide physical separation between target-complementary segments, carry detectable labels, and maintain probe flexibility. This multi-functionality reduces the need for additional separate components.
3Measurement precision
If multiple detectable labels are incorporated into the probe, then detectability is enhanced, but the ease of operation for secondary detection reagents is reduced
Solution Approach 1:
The spacer segments act as intermediaries that carry detectable labels in a configuration that facilitates access by secondary detection reagents. The spacer sequence and structure are designed to allow reagent binding while maintaining label detectability.
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 detectability of the probes by allowing dense labeling of spacer segments without affecting sequence specificity, facilitating easier access for secondary detection reagents and improving the accuracy of HPV detection in cervical cell specimens.
Implementation Method 1
a series of first nucleic acid segments consecutively complementary to a preselected nucleic acid target sequence
Implementation Method 2
at least some nucleic acid monomers of the spacer segments are labeled with detectable labels, such as fluorescent moieties or haptens
Data Source
AI summary
The invention provides nucleic acid hybridization probes having improved detectability that include a plurality of first segments consecutively complementary to a target nucleic acid sequence and, between neighboring first segments, a nucleic acid spacer segment which is not complementary to the target nucleic acid sequence and which may include labeled nucleic acid residues. Also provided by the invention are methods for making the probes, methods for using the probes, and compositions of matter that include the probes hybridized to target nucleic acid molecules.