Humanized VEGF Transgenic Mice for Angiogenesis Research
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Solution Overview
Problem
Current animal models are lacking for studying human VEGF, which is crucial for understanding its role in angiogenesis and developing therapeutic strategies for diseases such as cancer, limiting the availability of relevant models for drug development and disease study.
Innovation Solution
The development of transgenic mice expressing humanized VEGF, allowing for the study of VEGF-directed therapies and the use of these animals to screen agents targeting VEGF, including antibodies, to treat related diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If transgenic mice expressing humanized VEGF are developed, then the relevance of animal models for studying human VEGF therapies is improved, but the complexity of the model system increases
Solution Approach 1:
The patent applies parameter changes by modifying the VEGF protein sequence parameters - specifically humanizing 10 amino acid residues in the mouse VEGF molecule to create humanized VEGF variants (hum-X and hum-I). This changes the molecular composition parameter while maintaining the overall protein structure and function, thereby improving model relevance without excessive complexity
Solution Approach 2:
The patent uses an intermediary approach by creating humanized VEGF as a intermediate form between fully mouse VEGF and fully human VEGF. This intermediate molecule serves as a bridge that allows mouse models to respond to human anti-VEGF therapies while maintaining the physiological context of a mouse system
2Ease of manufacture
If mouse VEGF is used in current animal models, then the simplicity of the model is maintained, but the applicability to human VEGF therapy study is limited
Solution Approach 1:
The patent applies local quality by making localized modifications to specific regions of the VEGF molecule - humanizing only the 10 amino acid residues that are critical for antibody binding and therapeutic interaction, while leaving the rest of the mouse VEGF structure intact. This localized humanization maintains model simplicity while improving therapeutic applicability
Data Source
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AI summary
The present invention generally relates to humanized VEGF and non-human transgenic animals expressing it. The transgenic animals are also useful to study VEGF-related therapies.