Humanized SIRPα CD47 Mouse Models for Accurate Drug Screening
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Solution Overview
Problem
Conventional drug development methods using in vitro screening and conventional experimental animals fail to accurately replicate human disease states and tumor microenvironments, leading to high failure rates and discrepancies between animal trial results and clinical outcomes.
Innovation Solution
Development of genetically modified immunodeficient animal models expressing human or chimeric SIRPα and CD47 proteins, which can be used for drug screening and evaluation, mimicking human immune responses and tumor interactions more accurately.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional experimental animals are used for in vivo pharmacological tests, then the complexity of the animal model is reduced, but the accuracy of reflecting human disease states and treatment responses deteriorates
Solution Approach 1:
The patent creates a copy of the human immune system by introducing human genes (CD47, SIRPα, PD-1, CTLA-4) into immunodeficient mice, allowing the animal model to replicate human disease states and treatment responses more accurately while maintaining the simplicity of mouse physiology
Solution Approach 2:
The patent combines elements from different species to create a composite animal model: the mouse provides the basic physiological framework, while human genes are introduced to create chimeric protein expressions, resulting in a hybrid system that reflects human disease states without requiring a fully human organism
2Reliability
If in vitro screening approaches are used for drug development, then the complexity of the testing system is reduced, but the reliability of predicting in vivo outcomes deteriorates
Solution Approach 1:
The patent creates a living copy of the human tumor microenvironment within the mouse model, incorporating human tumor cells, immune cells, and stromal components to reliably predict in vivo outcomes while maintaining a manageable testing system
3Measurement precision
If genetically modified humanized animal models are developed, then the accuracy of drug screening and evaluation is improved, but the complexity of model preparation and maintenance increases
Solution Approach 1:
The patent uses gene targeting technology to create precise copies of human gene sequences at specific loci in the mouse genome, enabling accurate drug screening while maintaining a standardized model preparation process that can be replicated
Solution Approach 2:
The patent modifies specific genetic parameters (introducing human genes at defined loci with controlled expression levels) to achieve accurate drug screening capabilities while maintaining manageable model complexity through precise genetic engineering rather than comprehensive system replacement
Data Source
AI summary
This disclosure relates to genetically modified immunodeficient animals which express a human or chimeric (e.g., humanized) SIRPα and/or human or chimeric (e.g., humanized) CD47, and methods of use thereof.