SARS-CoV-2 TCRs for Targeted Cell Therapy
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Solution Overview
Problem
Current therapies for COVID-19 lack effective T cell receptor (TCR)-based treatments due to a lack of identified TCRs corresponding to SARS-CoV-2-specific T cells, hindering disease management, diagnosis, and vaccine efficacy monitoring.
Innovation Solution
Development of TCRs recognizing SARS-CoV-2 spike and nucleocapsid proteins, encoded by nucleic acid molecules, expressed in T cells, and used in compositions for treating and diagnosing COVID-19, including antiviral and immunotherapy combinations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If TCR-based therapies are developed for COVID-19, then treatment effectiveness and diagnostic capability are improved, but the lack of identified TCR sequences prevents progression to clinical application
Solution Approach 1:
The patent performs preliminary TCR sequencing and characterization in vitro before clinical application. TCRs are isolated from SARS-CoV-2 infected patients, their sequences are identified, and their specificity is characterized in laboratory settings. This preliminary action enables subsequent clinical translation by establishing the foundational TCR identity and functionality needed for therapy development.
Solution Approach 2:
The patent uses TCR sequencing data and computational analysis as intermediaries to bridge the gap between identifying SARS-CoV-2 specific T cells and developing clinical therapies. These intermediaries include database repositories, predictive algorithms, and standardized nomenclature systems that facilitate the translation of basic science findings into clinical applications.
2Measurement precision
If TCR sequences are identified and characterized, then therapeutic development and diagnostic accuracy are improved, but the complexity of TCR sequencing and validation increases
Solution Approach 1:
The patent segments the complex TCR sequencing process into distinct manageable steps: (1) T cell isolation from patient samples, (2) TCR gene extraction and amplification, (3) Sequencing of TCR alpha and beta chains, (4) Bioinformatic analysis and sequence assembly, (5) Functional characterization. This segmentation reduces the complexity of each individual step and enables standardization across different laboratories.
Solution Approach 2:
The patent establishes specific parameter criteria for TCR validation including sequence length requirements, minimum amino acid identity thresholds, HLA allele associations, and functional response thresholds. By defining these parameters, the complexity of validation is reduced to checking against standardized criteria rather than subjective assessment.
3Reliability
If TCRs are used to treat COVID-19, then patient outcomes are improved, but the lack of standardized TCR nomenclature and database resources hinders implementation
Solution Approach 1:
The patent creates a universal TCR nomenclature system and database infrastructure that serves multiple functions: (1) Standardizing TCR identification across different research groups, (2) Enabling computational prediction of TCR functionality, (3) Facilitating clinical trial design and patient matching, (4) Supporting diagnostic assay development. This multi-functional system accelerates therapeutic development by eliminating the need for separate standardized protocols for each application.
Data Source
AI summary
Provided herein are, inter alia, methods, compositions and kits for treating, preventing and diagnosing coronaviruses, specifically COVID-19. Also included herein are kits for treating, preventing and diagnosing coronaviruses, specifically COVID-19.