Production Cell Engineering by Removing Endogenous Protein Load
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Solution Overview
Problem
The high cost associated with the production of recombinant therapeutic proteins in mammalian cell expression systems hinders the global health industry, necessitating improved methods to increase yield and quality.
Innovation Solution
Reducing the level of non-essential, redundant, and/or secreted endogenous proteins in production cells through genetic modifications such as deletions, substitutions, or insertions, or using siRNA to target regulatory nucleic acid sequences, thereby optimizing the cellular environment for recombinant polypeptide production.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If endogenous proteins are reduced through genetic modifications or siRNA, then product yield and quality improve, but cell complexity and manufacturing difficulty increase
Solution Approach 1:
The patent applies the 'Taking out' principle by removing non-essential endogenous proteins from the host cell through genetic modifications (deletions, substitutions, insertions) or siRNA-mediated knockdown. This extraction of redundant cellular components redirects metabolic resources and cellular machinery toward recombinant polypeptide production, thereby increasing product yield without fundamentally altering the core cellular functions required for viability and production.
2Productivity
If endogenous proteins are reduced to increase product yield, then manufacturing cost decreases, but process complexity increases
Solution Approach 1:
The patent employs the 'Preliminary action' principle by pre-modifying host cells through genetic engineering or siRNA introduction before large-scale production. These modifications are performed during cell line development and stabilization phases, allowing the optimized cell lines to naturally produce higher yields during subsequent manufacturing processes without requiring complex real-time interventions or additional processing steps during production.
3Productivity
If non-essential endogenous proteins are reduced, then resource allocation for recombinant polypeptide production improves, but cell viability and growth may be affected
Solution Approach 1:
The patent applies the 'Local quality' principle by selectively reducing specific non-essential endogenous proteins while preserving essential cellular functions. Through careful selection of target proteins for reduction (those that are non-essential, redundant, or secreted), the patent locally optimizes resource allocation toward recombinant polypeptide production without globally compromising cell viability or essential metabolic pathways.
Data Source
AI summary
The present disclosure features methods, cells or cell lines, and compositions for increasing the amount of products, e.g., proteins, produced by a cell or cell line by reducing the level of a non-essential endogenous protein.