Engineered Cell Barcode Locus for Tracking Variant Combinations
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Solution Overview
Problem
Current methods are limited in producing and tracking higher-order combinations of genetic variants in a pooled format, which are critical for understanding how variants interact to modulate phenotype.
Innovation Solution
A method for introducing combinations of genetic variants into cells by sequentially building a unique barcode at a common locus, enabling tracking of each variant combination through sequencing-based counts, applicable to any genetic modification process.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If sequential barcode integration method is used, then tracking precision of variant combinations is improved, but device complexity increases
Solution Approach 1:
The patent divides the tracking system into modular components: a standardized barcode locus in the genome, sequential integration of individual barcodes representing different genetic variants, and independent gene editing agents. Each barcode is a discrete segment that can be tracked separately, enabling precise measurement of variant combinations without requiring a monolithic complex system
Solution Approach 2:
The patent adds a temporal dimension to barcode integration by sequentially adding barcodes at different time points rather than integrating all variants simultaneously. This sequential approach in the time dimension enables tracking of higher-order combinations while managing system complexity through staged implementation
2Adaptability or versatility
If arbitrary number of genetic changes are tracked, then adaptability is improved, but manufacturing precision deteriorates
Solution Approach 1:
The patent creates a universal barcode locus that can accommodate any number of barcodes representing different genetic variants. The same integration mechanism and barcode structure are used regardless of the specific variant being tracked, enabling the system to adapt to arbitrary numbers of genetic changes while maintaining consistent manufacturing precision through standardized protocols
Solution Approach 2:
The patent establishes a pre-defined barcode locus and standardized barcode structures before beginning variant tracking. This preliminary setup creates a scalable framework where additional barcodes can be integrated sequentially without requiring redesign, maintaining precision while adapting to varying numbers of genetic modifications
3Productivity
If higher-order combinations of genetic variants are produced, then productivity is improved, but device complexity increases
Solution Approach 1:
The patent enables continuous productivity improvement by allowing sequential rounds of barcode integration without resetting the system. Each round adds another layer of genetic variant tracking to the existing barcode array, maintaining continuous useful action while accumulating tracking capability. The same gene editing agents and integration mechanisms are reused across rounds, managing complexity through iterative refinement rather than complete system redesign
Data Source
AI summary
Described herein are methods for making genetically modified cells by introducing combinations of genetic variants (designed or random) or constructs (genes or otherwise arbitrary DNA) into a population of cells, and for tracking each variant combination by sequentially building an array of barcodes at a common locus (chromosomal or plasmid), termed the barcode locus. Also described are the cells made by such methods.