Mouse Artificial Chromosome Vectors for Stable Rodent Retention
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Solution Overview
Problem
Existing mouse artificial chromosome vectors face issues such as unstable retention rates, variations between tissues or individuals, and inconsistent progeny transmission, making it difficult to achieve stable gene expression and reproducible analyses, particularly when introduced into mouse cells.
Innovation Solution
Development of mouse artificial chromosome vectors derived from mouse chromosomes 10 and 16, featuring a natural centromere and a long-arm fragment with minimal endogenous genes, along with a telomere sequence, ensuring stable retention and transmission in rodent cells and tissues, and incorporating DNA sequence insertion sites for exogenous gene expression.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If human artificial chromosome vectors are introduced into mouse cells, then the vector can be used for production of human antibodies and drug metabolism testing, but the retention rate decreases and progeny transmission becomes unstable
Solution Approach 1:
The patent changes the chromosomal origin parameter from human to mouse, specifically using mouse chromosome 11 as the basis for constructing the artificial chromosome vector. This parameter change ensures compatibility with mouse cell machinery for replication and maintenance, thereby achieving stable retention and consistent progeny transmission while maintaining the vector's utility for human antibody production and drug metabolism testing in mouse models
2Reliability
If mouse artificial chromosome vectors from mouse chromosome 11 are used, then retention stability is improved, but information on chromosome structure is limited and trial-and-error is required
Solution Approach 1:
The patent performs preliminary characterization of mouse chromosome 11 structure, including identifying centromere regions, telomere sequences, and gene distribution patterns. This advance preparation of structural information eliminates the need for trial-and-error approaches in subsequent vector construction, as researchers now have a reference framework for designing stable mouse artificial chromosome vectors with proper structural elements
Solution Approach 2:
The patent segments the mouse chromosome 11 into functional regions (centromere, telomere, gene-rich regions, gene-poor regions) and analyzes each segment's contribution to vector stability. This segmentation approach identifies essential structural elements that must be included in artificial chromosome vectors, simplifying the manufacturing process by providing a checklist of required components
3Adaptability or versatility
If different mouse chromosome-derived vectors are used, then vector diversity is increased, but differences in chromosome structure lead to variations in nuclear position and gene expression control
Solution Approach 1:
The patent systematically varies the chromosomal origin parameter by constructing artificial chromosome vectors from multiple mouse chromosomes (chromosome 11, chromosome 16, and others). By controlling and standardizing other parameters such as centromere structure, telomere sequences, and inserted gene cassettes, the patent identifies that chromosome 11-derived vectors provide optimal balance between diversity and consistent expression control, with predictable nuclear positioning and gene expression patterns
Data Source
AI summary
A mouse artificial chromosome vector is stable in rodent cells, tissues, and/or individuals, specifically a mouse artificial chromosome vector derived from a mouse chromosome selected from mouse chromosome 10 and mouse chromosome 16. A cell or a non-human animal may include the vector. The vector may be used for producing proteins and human antibodies.