Automated Cell Surface Display Library for High-Throughput Binding Identification
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Solution Overview
Problem
Current methods for identifying specific binding partners, such as antibodies and antigens, in drug discovery and protein characterization are not robust enough for high-throughput, multiplexed analysis.
Innovation Solution
The development of automated methods for creating cell surface display libraries using multiplexed nuclease-directed genome editing, allowing for the expression and display of engineered peptides on cell surfaces, which can be screened for binding properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If traditional methods are used for identifying binding partners, then the process can be performed with existing technology, but the throughput and multiplexing capability are insufficient for high-throughput analysis
Solution Approach 1:
The invention segments the binding partner identification process into multiple parallel tracks, each representing a different binding partner or molecular target. This segmentation enables simultaneous analysis of multiple targets across different cell populations, achieving high throughput while maintaining manageable complexity through modular design
Solution Approach 2:
The invention introduces a multiplexing dimension by enabling simultaneous detection of multiple binding partners through fluorescent labeling and flow cytometry. This dimensional expansion from single-target to multi-target analysis significantly increases productivity without proportionally increasing operational complexity
2Productivity
If cell surface display libraries are created using automated multiplexed nuclease-directed genome editing, then high-throughput identification is achieved, but the method complexity and automation requirements increase
Solution Approach 1:
The invention employs self-service automation where the nuclease-directed genome editing system automatically performs multiple functions including target selection, library generation, and phenotypic screening. The system self-regulates the entire workflow from DNA manipulation to cell surface display, reducing manual intervention while maintaining high throughput
Solution Approach 2:
The invention replaces manual mechanical operations with automated nucleic acid-directed enzymatic processes. The nuclease-based editing system substitutes for traditional manual cloning and screening methods, enabling high-throughput automation through biochemical mechanisms rather than mechanical manipulation
3Measurement precision
If engineered peptides are displayed on cell surfaces for binding analysis, then specific binding partners can be identified, but the cell population engineering complexity increases
Solution Approach 1:
The invention applies local quality by displaying specific engineered peptides on the cell surface at controlled locations and densities. This localized presentation of binding partners enables precise identification of specific interactors while keeping the overall cell population engineering manageable through targeted modification rather than global transformation
Data Source
AI summary
The present disclosure methods for identifying binding partners using cell surface display libraries, where the cells of the library display engineered peptides on their cell surfaces for identification of peptides that bind to targets of interest. The engineered peptides are preferably expressed in the cells under conditions that provide both secretion and display of the engineered peptides on the cell surfaces, thus providing access of the engineered peptides to identify potential binding pairs. The cell libraries cab be engineered using an automated editing system that provides for one or more targeted edits per cell.