Quantitative Ligandomics for Systematic Ligand Identification
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Solution Overview
Problem
Current methods are inefficient in systematically identifying disease-specific, age-related, and receptor-specific cellular ligands, hindering the development of ligand-based therapies due to low efficiency in manually screening phage clones and inability to globally quantify binding or functional activity of ligands.
Innovation Solution
Combining phage display, particularly open reading frame (ORF) phage display, with next-generation DNA sequencing (NGS) for quantitative ligandomics to globally identify ligands with simultaneous binding or functional activity quantification, enabling systematic comparison of ligandome profiles between diseased and healthy cells or aged and young cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional phage display is used to identify cellular ligands, then ligands can be identified on a case-by-case basis, but the process is inefficient and cannot systematically identify disease-specific or age-related ligands
Solution Approach 1:
The patent combines phage display technology with next-generation sequencing (NGS) to create a high-throughput system that merges the ligand identification capability of phage display with the parallel sequencing power of NGS, enabling systematic identification of multiple ligand types simultaneously
Solution Approach 2:
The patent creates a universal ligandomics platform that can identify multiple types of ligands (cell-wide ligands, disease-associated ligands, age-related ligands, and receptor-specific ligands) using the same methodology, making the system adaptable to various research questions
2Measurement precision
If traditional manual screening of phage clones is used, then ligands can be identified, but the binding or functional activity of ligands cannot be globally quantified
Solution Approach 1:
The patent replaces manual mechanical screening of phage clones with automated next-generation sequencing technology, substituting labor-intensive processes with high-throughput molecular biology methods that provide both quantitative data and parallel processing capability
Solution Approach 2:
The patent uses NGS to create digital copies and counts of phage clone sequences, allowing quantitative measurement of ligand binding activity through sequence frequency analysis rather than manual counting or functional assays
3Reliability
If case-by-case identification of disease-associated ligands is performed, then specific ligands can be found, but the process is time-consuming and hinders reliable selection of drug targets
Solution Approach 1:
The patent performs preliminary global identification and quantification of all cellular ligands in a single experiment, creating a comprehensive ligandome profile that can be reused for multiple disease comparisons, eliminating the need for repeated case-by-case identification
Solution Approach 2:
The patent segments the ligand identification process into distinct comparative analyses (healthy vs. diseased, young vs. aged) that can be performed independently on the same dataset, allowing systematic identification of different ligand categories without repeating the entire identification process
Data Source
AI summary
The present invention is directed to methods for developing novel anti-angiogenic therapies. This invention discovers secretogranin III (Scg3) not only as a novel disease-selective angiogenic factor but also as a target for anti-angiogenic therapy of vascular diseases. Inhibitors against Scg3 can treat diabetic retinopathy, wet age-related macular degeneration, retinopathy of prematurity, retinal vein occlusion, neovascular glaucoma, corneal neovascularization, and cancers.