Mouse Artificial Chromosome Vector for Stable Rodent Inheritance
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing mouse artificial chromosome vectors face issues such as unstable retention and transmission, inconsistent gene expression, and lack of information on chromosome structure, leading to difficulties in preparing stable vectors for rodent cells and progeny transmission.
Innovation Solution
Development of mouse artificial chromosome vectors derived from mouse chromosomes 10 and 16, featuring a natural centromere, a truncated long-arm region with minimal endogenous genes, and a telomere sequence, ensuring stable retention and transmission in rodent cells and tissues.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If human artificial chromosome (HAC) vectors are introduced into mouse cells, then the vectors 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, creating mouse artificial chromosome (MAC) vectors derived from mouse chromosome 10 or 16. This parameter change ensures compatibility with mouse cellular machinery, including centromere-cytokinesis coupling and telomere maintenance mechanisms, thereby achieving both high retention rates and stable progeny transmission while maintaining versatility for antibody production and drug metabolism testing
Solution Approach 2:
Instead of introducing human chromosomes into mouse cells (HAC approach), the patent inverts the approach by introducing mouse chromosomes into mouse cells (MAC approach). This inversion resolves the incompatibility issues by making the artificial chromosome homologous to the host genome, enabling proper segregation during cell division and stable inheritance across generations
2Adaptability or versatility
If trial-and-error methods are used to prepare MAC vectors from unknown chromosome structures, then various MAC vectors can be explored, but the preparation process becomes complex and time-consuming
Solution Approach 1:
The patent performs preliminary characterization of mouse chromosome 10 and 16 structures, including identification of centromere regions, telomere sequences, and gene distributions, before constructing MAC vectors. This preliminary action provides a roadmap for vector design, eliminating the need for trial-and-error approaches and significantly reducing preparation complexity while enabling systematic exploration of different chromosome-derived vectors
Solution Approach 2:
The patent segments the chromosome construction process into defined modules: centromere region selection, telomere sequence attachment, and gene content organization. By segmenting the complex chromosome structure into manageable components with known functions, the patent simplifies the overall preparation process while maintaining the ability to create diverse MAC vector variants
3Adaptability or versatility
If HAC vectors are used in mouse cells, then human antibody production is enabled, but gene expression dynamics cannot be accurately analyzed at cell or tissue level
Solution Approach 1:
The patent changes the chromosomal origin parameter from human to mouse, creating MAC vectors that are homologous to the host genome. This enables accurate measurement of gene expression dynamics at cell and tissue levels through standard mouse molecular biology techniques, while simultaneously maintaining the capability for human antibody production by introducing human immunoglobulin genes into the mouse artificial chromosome structure
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.