Engineered CHO Cells Removing Endogenous Retrovirus Elements
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current mammalian cell lines used in recombinant protein manufacturing, such as CHO cells, contain remnants of infectious viral particles that pose safety concerns and require labor-intensive characterization, leading to regulatory challenges and potential risks in therapeutic protein production.
Innovation Solution
Engineered CHO cells with altered genomes that suppress or eliminate endogenous retrovirus elements, using CRISPR/Cas9 systems to introduce deletions, additions, or substitutions in ERV elements, thereby reducing the release of viral particles and enhancing safety profiles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CHO cells are used for therapeutic protein production, then stable host capability and human-like post-translational modification are achieved, but viral remnants lead to safety concerns and regulatory documentation requirements
Solution Approach 1:
The patent applies the extraction principle by removing harmful viral remnants (endogenous retrovirus elements) from the CHO cell genome through targeted gene editing. CRISPR/Cas9 systems are used to specifically excise or disable ERV sequences, thereby extracting the harmful component while preserving the beneficial characteristics of CHO cells for protein production
Solution Approach 2:
The patent converts the harmful presence of ERV elements into a benefit by using them as targets for CRISPR/Cas9-mediated genome editing. The ERV sequences, which would normally be harmful, become useful markers for guiding the editing machinery to improve cell safety while maintaining production capabilities
2Reliability
If comprehensive characterization of CHO cell genomes is performed to detect viral remnants, then safety assessment is improved, but time consumption and cost increase
Solution Approach 1:
The patent applies preliminary action by proactively engineering CHO cells to eliminate viral remnants before they can cause safety issues or require extensive detection. The CRISPR/Cas9 editing is performed in advance during cell line development, preventing the need for lengthy characterization processes later in regulatory approval
Solution Approach 2:
The patent replaces complex mechanical characterization processes with a more efficient molecular biology approach. Instead of using labor-intensive methods to detect and characterize viral remnants, the invention uses CRISPR/Cas9 genome editing to directly modify and eliminate the harmful elements, streamlining the safety assessment process
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The engineered cells significantly reduce the expression and release of viral particles, improving safety and regulatory compliance by minimizing the risk of adventitious agents, and facilitating more efficient and cost-effective candidate drug development and production.
Implementation Method 1
using CRISPR/Cas9 systems to introduce deletions, additions, or substitutions in ERV elements
Data Source
AI summary
Disclosed are mammalian cells and mammalian cell lines that have a reduced load of remnants of past viral/retroviral infections and methods of producing and using the same.