Human Antibody Production via Mouse Artificial Chromosome
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for producing human antibodies in transgenic animals are inefficient, with low stability and transmission rates to progeny, and often require complex chromosome engineering techniques.
Innovation Solution
Development of a non-human animal, such as a mouse, equipped with a mouse artificial chromosome (MAC) carrying human antibody heavy and light chain genes, combined with endogenous antibody gene knockout techniques to stabilize human antibody production and transmission.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional transgenic animal methods are used to produce human antibodies, then human antibodies can be produced in non-human animals, but the production efficiency is low and stability is poor
Solution Approach 1:
The patent segments the human antibody genes into distinct components (heavy chain genes and light chain genes) and inserts them separately into the mouse artificial chromosome at specific loci (IgH and IgK loci). This segmentation allows for proper gene rearrangement and expression while maintaining stability during transmission to progeny, thereby improving both production efficiency and stability.
Solution Approach 2:
The patent uses a mouse artificial chromosome (MAC) as an intermediary carrier to deliver and maintain human antibody genes in non-human animals. The MAC serves as a stable intermediary structure that preserves human antibody genes through generations while enabling their expression, thus resolving the contradiction between production efficiency and stability.
2Productivity
If chromosome engineering techniques are used to prepare human antibody-producing animals, then human antibodies can be produced, but the process complexity increases
Solution Approach 1:
The patent merges multiple human antibody gene components (heavy chain and light chain genes) into a single integrated structure on the mouse artificial chromosome. This consolidation simplifies the overall genetic engineering process compared to manipulating multiple separate chromosomes or genomic locations, thereby reducing process complexity while maintaining production capability.
Solution Approach 2:
The patent uses the mouse artificial chromosome as a copyable, transmissible carrier that replicates human antibody genes faithfully during cell division and transmission to progeny. This copying mechanism eliminates the need for complex repeated engineering interventions, simplifying the process while ensuring stable human antibody production.
3Productivity
If human antibody genes are introduced into non-human animals, then human antibodies can be produced, but transmission to progeny is unstable
Solution Approach 1:
The patent performs preliminary integration of human antibody genes into the mouse artificial chromosome structure before introduction into the host animal. The genes are pre-positioned at appropriate loci with proper regulatory elements, ensuring stable inheritance and expression in progeny without requiring further complex engineering, thus improving transmission stability while maintaining production capability.
Data Source
AI summary
This application provides: a non-human animal that comprises a mouse artificial chromosome comprising a human antibody heavy chain gene or gene locus, a human antibody light chain κ gene or gene locus, and/or a human antibody light chain λ gene or gene locus, and in which endogenous antibody genes or gene loci corresponding to at least 2 human antibody genes or gene loci have been knocked out, wherein the animal can be stably retained through generations and can produce human antibodies; a method for producing the non-human animal; and a method for producing human antibodies using the non-human animal.