Hypoimmunogenic Cell Engineering via Targeted Gene Expression Reduction
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Solution Overview
Problem
Current cell therapy approaches face challenges such as chemical and molecular interference, cell-to-cell interference, competition for nutrients, cellular exhaustion, and manufacturing issues, leading to a dearth in cell therapy approvals for targeting complex diseases like neoplasia and cancers.
Innovation Solution
Genetically modify regulatory factor X (RFX) and other genes in immunogenic human cells to reduce protein expression, forming hypoimmunogenic cells through embryoid bodies, which exhibit reduced immunogenicity and immune responses, thereby addressing challenges in cell therapy approvals.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If genetically modified RFX and other genes are modified to reduce protein expression, then immunogenicity is reduced, but manufacturing complexity increases
Solution Approach 1:
The patent segments the immunogenicity reduction process into multiple independent genetic modifications (RFX, CIITA, B2M, CD58 genes modified separately), allowing each modification to be optimized and controlled independently while collectively achieving hypoimmunogenicity without proportionally increasing overall manufacturing complexity
Solution Approach 2:
The patent changes the expression parameters of specific genes (RFX, CIITA, B2M, CD58) to reduce protein expression levels, thereby reducing immunogenicity. This targeted parameter change approach allows precise control over immunogenicity reduction while maintaining manageable manufacturing processes
2Reliability
If cell therapy approaches are used to target complex diseases, then therapeutic efficacy is improved, but immune rejection and cellular exhaustion increase
Solution Approach 1:
The patent applies preliminary anti-action by pre-modifying the RFX, CIITA, B2M, and CD58 genes in the therapeutic cells before administration. This preliminary genetic modification creates hypoimmunogenic cells that proactively resist immune rejection and cellular exhaustion, allowing the cells to maintain therapeutic efficacy longer without being attacked by the host immune system
Data Source
AI summary
Provided herein are methods of hypoimmunogenicity, such as bioengineering methodologies and materials, including hypoimmunogenicity (such as engineering hypoimmunogenicity) methodologies and materials useful in, for example, genetically modifying and/or otherwise altering at least one target gene or gene product, processes for producing engineered hypoimmunogenic cells, manufacturing of engineered hypoimmunogenic cellular compositions, and uses thereof.