Humanized TSLP Pathway Rodent Models for Allergy and Cancer Research
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Solution Overview
Problem
Existing systems lack effective in vivo models for understanding the pathogenesis of allergic diseases and cancer, limiting the development of targeted therapeutics.
Innovation Solution
Genetically modify rodents with humanized Tslp, Tslpr, and/or Il7ra genes to create animal models that express human TSLP, TSLPR, and IL7RA proteins, allowing for better study of allergic diseases and cancer.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If rodent models are used for studying allergic diseases and cancer, then the model is simple and easy to maintain, but the pathogenesis understanding is inaccurate due to species differences in TSLP pathway proteins
Solution Approach 1:
The patent applies local quality by humanizing only the specific TSLP, TSLPR, and IL7RA genes in the rodent genome while leaving the rest of the genome unchanged. This targeted gene replacement approach introduces human protein sequences only where needed for the TSLP pathway, achieving accurate pathogenesis modeling without requiring complete humanization of the animal model.
Solution Approach 2:
The patent creates composite genetic structures by combining rodent genome background with human gene sequences. The resulting animal models have a hybrid composition: rodent genomic DNA with replaced human TSLP, TSLPR, and/or IL7RA genes, enabling the study of human disease pathogenesis in a rodent system with improved reliability.
2Measurement precision
If humanized genes are introduced to improve model accuracy, then the pathogenesis study accuracy improves, but the manufacturing complexity of the animal model increases
Solution Approach 1:
The patent segments the complex task of creating accurate disease models by targeting specific individual genes (TSLP, TSLPR, IL7RA) for humanization. This allows for stepwise generation of animal models, where researchers can choose to humanize one gene at a time or combine multiple gene humanizations, making the manufacturing process more manageable and flexible.
Solution Approach 2:
The patent changes the genetic parameters of the rodent model by replacing specific gene sequences with their human counterparts. This parameter change at the DNA level results in altered protein expression patterns that more accurately reflect human disease pathogenesis, while the underlying rodent physiology remains intact for ease of maintenance.
Data Source
AI summary
Disclosed herein are rodents (such as, but not limited to, mice and rats) genetically modified to comprise a humanized Tslp gene, a humanized Tslpr gene, a humanized Il7ra gene, or a combination thereof. Compositions and methods for making such genetically modified rodents, as well as methods of using such genetically modified rodents as an animal model for diseases such as allergic diseases and cancer are provided.