Humanized CD47 Mouse Model for Accurate Drug Screening
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Solution Overview
Problem
Traditional drug development methods for immune-related diseases and cancer therapies face challenges due to the inability of conventional animal models to accurately mimic human tumor microenvironments, leading to high failure rates and discrepancies between animal trial results and clinical outcomes.
Innovation Solution
The development of genetically modified animal models that express human or chimeric CD47, allowing for the creation of a platform for drug screening and evaluation that more accurately reflects human immune responses and tumor interactions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional animal models are used for drug screening, then the cost and time for drug development are reduced, but the accuracy and reliability of test results decrease due to species differences and inability to mimic human tumor microenvironment
Solution Approach 1:
The patent applies local quality by partially humanizing the animal model - specifically replacing the mouse CD47 gene with the human CD47 gene while keeping the rest of the mouse genome intact. This creates a localized human-like feature (human CD47 expression) in a non-human animal system, allowing accurate testing of anti-CD47 antibodies without requiring complete humanization of the entire organism.
Solution Approach 2:
The patent uses a genetically modified mouse as an intermediary system between complete mouse models and human clinical trials. The humanized CD47 mouse serves as a middle ground that expresses human CD47 protein and interacts with human anti-CD47 antibodies, bridging the gap between species-specific mouse models and human patients.
2Reliability
If humanized animal models are developed to improve test accuracy, then the reliability of drug screening increases, but the complexity and cost of model development increase
Solution Approach 1:
The patent implements local quality by targeting only the specific CD47 gene locus for humanization while maintaining the simplicity of the mouse model for all other physiological systems. This focused approach allows reliable drug screening for CD47-targeted therapies without the complexity of creating a fully humanized animal model.
Solution Approach 2:
The patent segments the CD47 gene into specific exons (exons 2-10) for replacement, allowing precise genetic modification. The humanized CD47 construct is designed to include specific functional domains while maintaining compatibility with the mouse genomic context, facilitating easier model development and maintenance.
Data Source
AI summary
The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) CD47, and methods of use thereof.