Repebody Polypeptide Binds VEGF to Inhibit Angiogenesis
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Solution Overview
Problem
Current antibody therapeutic agents for treating diseases like age-related macular degeneration and cancer face challenges such as high production costs, difficulty penetrating cells due to large molecular weight, and limited therapeutic efficacy, prompting the need for alternative therapeutic agents with improved specificity and binding affinity.
Innovation Solution
A novel polypeptide is developed using a repebody scaffold, specifically designed to bind to vascular endothelial growth factor (VEGF) by fusing an N-terminal leucine-rich repeat (LRR) family protein with an alpha-helical capping motif and a C-terminal variable lymphocyte receptor (VLR) protein, with targeted mutations at specific amino acid positions, which is produced using a recombinant microorganism and used to inhibit VEGF activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If antibody therapeutic agents are used to treat diseases like age-related macular degeneration and cancer, then high treatment efficacy is achieved, but production cost becomes high and it is difficult to escape existing patent barriers
Solution Approach 1:
The patent creates a simplified copy of the antibody therapeutic agent by using a peptide-based small molecule that replicates the binding function of large antibodies against VEGF, thereby achieving similar therapeutic efficacy at lower production cost and without patent barriers
Solution Approach 2:
The patent employs a small peptide molecule that is cheaper to produce than antibodies, accepting that it may have shorter half-life or require more frequent administration, thereby reducing overall treatment cost while maintaining efficacy
2Reliability
If antibody therapeutic agents are used, then high treatment efficacy is achieved, but penetration into cells is difficult due to large molecular weight
Solution Approach 1:
The patent segments the large antibody molecule into a much smaller peptide fragment that retains the essential VEGF-binding capability, enabling penetration into cells and tissues that are inaccessible to full-size antibodies
3Ease of manufacture
If existing VEGF-targeting drugs like Bevacizumab are used, then treatment of age-related macular degeneration is achieved, but binding affinity and therapeutic efficacy are lower compared to other monoclonal antibody drugs
Solution Approach 1:
The patent optimizes the peptide sequence and structural parameters to achieve picomole-level binding affinity to VEGF, significantly improving upon the nanomole-level affinity of existing drugs like Bevacizumab while maintaining the advantage of smaller size and lower cost
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The polypeptide effectively binds to VEGF, demonstrating high specificity and therapeutic efficacy in inhibiting choroidal neovascularization in animal models, offering a promising treatment for age-related macular degeneration and cancer by reducing vascular permeability and tumor growth.
Implementation Method 1
a polypeptide capable of binding to vascular endothelial growth factor to inhibit the activity thereof
Data Source
AI summary
The present disclosure relates to a novel polypeptide capable of binding specifically to vascular endothelial growth factor, a polynucleotide encoding the polypeptide, a vector comprising the polynucleotide, a recombinant microorganism including the expression vector, a method of producing the polypeptide using the recombinant microorganism, a composition for treating or preventing age-related macular degeneration or cancer, which comprises the polypeptide, and a method for preventing or treating age-related macular degeneration or cancer, which comprises administering the composition for treating or preventing age-related macular degeneration or cancer, which comprises the polypeptide. The disclosed polypeptide is capable of binding to vascular endothelial growth factor to inhibit the activity thereof, and thus can be widely used as an agent for treating and preventing various diseases associated with vascular endothelial growth factor (VEGF).