Eukaryotic Cells FAM60A Impairment Stable Expression
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Eukaryotic cell lines, particularly mammalian cells, face significant challenges in maintaining stable recombinant protein expression over time due to genetic instability and epigenetic silencing, leading to productivity losses, which prolongs the biotechnological production process and increases screening efforts.
Innovation Solution
Altering the genome of eukaryotic cells to impair the function of the FAM60A protein, either by reducing or eliminating its expression, results in increased stability and productivity of recombinant protein expression, allowing for the identification of stable clones earlier in the development process.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If extensive stability analyses are performed over several weeks to months to identify stable clones, then the reliability of production stability is improved, but the time required for clone selection and process development is significantly prolonged
Solution Approach 1:
The patent introduces a preliminary genetic modification (knockout of specific genes such as FAM60A, C12orf35, or telomeric regions) before the actual stability selection process. This preliminary action creates cell lines that are pre-configured to maintain stable expression, thereby reducing the time needed for extensive stability analyses while ensuring production reliability.
2Productivity
If high expressing clones are identified through screening, then the productivity is improved, but these clones often lose their advantageous expression characteristics over time due to instability
Solution Approach 1:
The patent segments the problem by separating the selection for high expression from the selection for stability. First, high expressing clones are identified through screening, then these clones are subjected to prolonged subculturing to test stability. Unstable clones are eliminated, and only those maintaining high expression after subculturing are selected for production, thus ensuring both productivity and stability.
Solution Approach 2:
The patent changes the genetic parameters of the host cell line by knocking out specific genes (FAM60A, C12orf35, or telomeric regions) to create a cellular environment that inherently supports stable expression. This parameter change in the host cell genetics allows high expressing clones to maintain their productivity over time without losing expression characteristics.
3Stability of the object's composition
If the genome is altered to impair FAM60A function, then the stability of recombinant protein expression is improved, but the device complexity and screening requirements increase
Solution Approach 1:
The patent extracts or removes specific problematic genetic elements (FAM60A gene, C12orf35 gene, or telomeric regions) from the host cell genome. By taking out these specific genes responsible for instability, the overall system becomes more stable for recombinant protein expression, despite the initial complexity of the genetic modification process.
Data Source
AI summary
The disclosure pertains to novel eukaryotic cell suitable for recombinant production of a product of interest, wherein the genome of the host cell is altered so that the effect of protein FAM60A is impaired in said cell, e.g. by reducing or eliminating functional expression of gene FAM60A thereby improving the stability characteristics. Furthermore, the present disclosure provides associated technologies wherein such host cells are used in recombinant production technologies.