HDLBP Co-expression Boosts Recombinant Protein Secretion
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Solution Overview
Problem
Current methods for producing secreted recombinant proteins in eukaryotic cells are inefficient, lacking strategies to optimize and enhance the expression and secretion of proteins such as therapeutic antibodies and hormones, which are crucial for biotechnology and biomedicine.
Innovation Solution
The method involves artificially co-expressing a protein with an amino acid sequence having at least 90% identity to specific sequences, such as those of HDLBP/Vigilin, in eukaryotic cells like CHO or HEK293, to enhance the expression and secretion of secreted recombinant proteins through overexpression of HDLBP, which interacts with ER-bound mRNAs and influences translation efficiency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If standard protein expression methods are used in eukaryotic cells, then the production process is simple, but the protein secretion efficiency is low
Solution Approach 1:
The patent introduces HDLBP/Vigilin as an intermediary protein that mediates between ER-bound mRNAs and the translation machinery. This intermediary facilitates enhanced protein secretion by interacting with mRNAs at the ER membrane, thereby resolving the contradiction between simple expression methods and low secretion efficiency without requiring complex system modifications
Solution Approach 2:
The patent changes the expression level parameter of HDLBP/Vigilin protein in the system. By overexpressing this specific protein component, the system achieves enhanced protein secretion efficiency (up to 290% increase) while maintaining the overall simplicity of the eukaryotic expression system, thus resolving the technical contradiction
2Productivity
If canonical SRP-dependent pathway is used for protein secretion, then the mechanism is well-understood, but the secretion capacity is limited
Solution Approach 1:
The patent performs preliminary action by pre-expressing HDLBP/Vigilin protein in the cell system before introducing the target protein expression. This preliminary establishment of the enhancement mechanism allows the canonical SRP-dependent pathway to operate at enhanced capacity without requiring fundamental pathway redesign, thus increasing secretion capacity while maintaining pathway simplicity
Solution Approach 2:
The HDLBP/Vigilin protein serves multiple functions: it interacts with ER-bound mRNAs, enhances translation efficiency, and boosts protein secretion. This multi-functional intermediary can be applied universally to enhance secretion of various proteins through the canonical pathway, increasing capacity without adding pathway complexity
Data Source
AI summary
The invention is related to a method for producing a secreted recombinant protein of interest in a cell, wherein the method comprises artificially co-expressing a protein different from the secreted recombinant protein of interest.