Co-Occurring Receptor Segment Detection via Probe Hybridization
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Solution Overview
Problem
Current methods struggle to identify co-occurring nucleic acid segments coding for functional T-cell receptor pairs in tumor tissue samples, particularly in solid tumors, due to the complexity of sequencing and the limited availability of surface markers, which hinders the development of effective immunotherapies for solid tumors.
Innovation Solution
The method involves obtaining nucleic acid samples from specimens, determining sequences of alpha and beta chain segments, generating probes linked to detection moieties, and performing hybridization analysis to identify co-occurring segments, enabling the engineering of T-cells with functional neoantigen-specific receptors for therapeutic applications.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If sequencing methods are used to identify T-cell receptor pairs, then nucleic acid segments can be analyzed, but the complexity of sequencing and limited surface markers make identification of co-occurring pairs challenging
Solution Approach 1:
The patent uses probes as intermediary molecules that hybridize to specific nucleic acid sequences. These probes serve as mediators between the complex sequencing data and the final identification of co-occurring T-cell receptor pairs, simplifying the detection process while maintaining high precision through specific hybridization events
Solution Approach 2:
The patent creates copies of nucleic acid sequences through probe hybridization and amplification steps. By generating detectable copies of the target sequences, the method enables precise identification of co-occurring pairs without requiring direct analysis of the original complex sequencing data
2Measurement precision
If probes are generated from determined sequences and hybridized to detection samples, then co-occurring segments can be precisely identified, but the process requires multiple steps including sequence determination, probe generation, and hybridization analysis
Solution Approach 1:
The patent divides the detection process into distinct segments: sequence determination, probe generation from determined sequences, hybridization to detection samples, and analysis of hybridization events. This segmentation allows each step to be optimized independently while maintaining overall precision in identifying co-occurring nucleic acid segments
Solution Approach 2:
The patent performs preliminary sequence determination and probe generation before the actual hybridization detection. By preparing probes in advance based on determined sequences, the method ensures high precision in co-occurrence detection while organizing the complex multi-step process into manageable preliminary and final phases
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 allows for the precise identification of functional T-cell receptor pairs, facilitating the engineering of T-cells that can be infused for targeted anti-tumor immune responses, potentially offering more effective therapeutic outcomes than conventional treatments.
Implementation Method 1
probes derived from a first sample or a first portion of a sample are hybridized to a second sample or a second portion of the sample, and detection of specific hybridization events associated with probes related to specific segment sequences
Data Source
AI summary
Methods for identifying co-occurrence of nucleic acid segments in a nucleic acid sample from a specimen including obtaining a nucleic acid sample from a specimen, determining sequences of first and second nucleic acid segments in nucleic acid fragments of the sample to generate a first and second sets of sequences, generating a first and second sets of probes from the first and second sets of sequences, exposing a detection sample to a member of the first set of probes and a member of the second set of probes, performing a hybridization analysis to determine whether the members of the first and second sets of probes hybridize to the detection sample, and determining whether the first and second nucleic acid segments co-occur in a common cell of the specimen.