Col8a1 Knockout Animal Models for VEGF-Resistant AMD
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Solution Overview
Problem
Current animal models for age-related macular degeneration (AMD) and other angiogenesis-related diseases are not responsive to VEGF inhibitors, making it difficult to develop therapies for non-responsive cases, and there is a need for improved models and methods to identify effective agents for treating these conditions.
Innovation Solution
The use of Collagen Type VIII Alpha 1 Chain (Col8a1) gene knockout or knockdown models in animals and cells to induce neovascularization, allowing evaluation of agents' efficacy in modulating angiogenesis and wound healing by measuring lesion size or tumor formation, with agents administered before, during, or after induction.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing mouse models of AMD are used, then the models are highly responsive to VEGF inhibitors, but this makes it difficult to screen for and study therapies that can treat AMD that is non-responsive to VEGF inhibitors
Solution Approach 1:
The patent introduces a genetic parameter change by knocking out or knocking down the Col8a1 gene in the mouse model. This parameter change fundamentally alters the model's response characteristics to VEGF inhibitors, transforming it from a highly responsive state to a non-responsive state that better reflects clinical reality and enables screening of alternative therapies.
2Reliability
If Col8a1 gene is knocked out or knocked down, then the model becomes non-responsive to VEGF inhibitors like human patients, but this requires complex genetic modification procedures
Solution Approach 1:
The patent uses Col8a1 gene knockout or knockdown as an intermediary mechanism to achieve the desired clinical accuracy. By targeting this specific gene as a mediator, the model reproduces human patient non-responsiveness to VEGF inhibitors without requiring more complex surgical or environmental modifications.
3Adaptability or versatility
If agents are administered to Col8a1 knockout subjects, then efficacy can be demonstrated in VEGF inhibitor-resistant cases, but this requires establishing multiple transgenic animal lines
Solution Approach 1:
The Col8a1 knockout or knockdown mouse model serves as a universal platform that can evaluate multiple different therapeutic agents for VEGF inhibitor-resistant AMD cases. This single model type can be used to screen various agents including anti-angiogenic therapies, making the system universally applicable rather than requiring separate models for each agent.
Data Source
AI summary
The present disclosure provides animal models of wound healing and diseases associated with angiogenesis, such as age-related macular degeneration (AMD), fibrosis and cancer. The present disclosure further provides methods for identifying agents for promoting wound healing, modulating angiogenesis or treating diseases associated with angiogenesis, such as AMD and cancer.