CRISPR VEGFA VHL Knockout for Angiogenesis Control
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Solution Overview
Problem
Current methods for treating diseases associated with excessive neovascularization, such as cancer and diabetic retinopathy, are inadequate, as they often lead to side effects like increased cancer cell aggression or lack fundamental treatment approaches.
Innovation Solution
An artificially manipulated neovascularization system using a genetically modified neovascularization-associated factor, like HIF1A, regulated by a guide nucleic acid-editor protein complex, to modulate neovascularization processes, either promoting or inhibiting the formation of new blood vessels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If VEGF signaling is inhibited to prevent neovascularization, then neovascularization is suppressed, but cancer cells become more aggressive and metastatic
Solution Approach 1:
The invention segments the VEGF signaling pathway into two distinct targets: VEGFA (involved in neovascularization) and VHL (involved in cancer cell aggression). By using CRISPR/Cas9 to simultaneously knock out both genes, the treatment selectively inhibits neovascularization while preventing the compensatory increase in cancer cell aggressiveness that occurs with conventional VEGF inhibition
Solution Approach 2:
The invention employs a composite therapeutic approach combining two genetic modifications (VEGFA knockout and VHL knockout) in a single treatment regimen. This dual-gene CRISPR strategy creates a synergistic effect where both pathways are simultaneously modulated to achieve superior clinical outcomes compared to single-target inhibition
2Object-affected harmful factors
If conventional VEGF inhibition is used to treat neovascularization, then initial neovascularization suppression is achieved, but side effects occur due to inhibited anticancer agent pathways
Solution Approach 1:
The invention divides the VEGF family into specific targets, selecting VEGFA for knockout while preserving other VEGF isoforms. This segmentation allows selective inhibition of pathological neovascularization while maintaining physiological functions mediated by other VEGF members, thereby reducing treatment side effects
Solution Approach 2:
The CRISPR/Cas9 system acts as an intermediary tool that enables precise genetic modification of VEGFA and VHL genes. This intermediary approach allows for permanent, specific gene knockout without the off-target effects associated with conventional small molecule inhibitors or monoclonal antibodies
Data Source
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AI summary
The present invention relates to artificially engineered angiogenesis-related factors and a use thereof, for angiogenesis regulation. More specifically, the present invention relates to a system that can artificially regulate angiogenesis, including artificially engineered angiogenesis-related factors to regulate angiogenesis and/or a composition capable of artificially engineering angiogenesis-related factors. In specific aspects, the present invention relates to artificially engineered angiogenesis-related factors such as VEGFA, HIF1A, ANGPT2, EPAS1, ANGPTL4, etc. and/or an angiogenesis regulatory system by their expression products thereof.