Transient Immortalizing Factors for Non-Genetically Modified Cell Expansion
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Solution Overview
Problem
Conventional animal agriculture for meat production faces challenges such as environmental degradation, zoonotic disease emergence, antimicrobial resistance, and animal welfare concerns, with cultured meat production being limited by scalability and high costs due to small-scale processes, and primary cells senescing shortly after extraction, necessitating non-genetically modified large-scale cell expansion methods.
Innovation Solution
The use of transient immortalizing factors like telomerase reverse transcriptase (TERT), cyclin-dependent kinase 4 (CDK4), and inhibitors of cellular senescence to temporarily induce immortalization in cells, allowing for prolonged proliferation without genetic modification, followed by removal of these factors to return cells to their original state.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If primary cells are extracted from host animals for cultured meat production, then the cells can be used to produce meat alternatives, but the cells senesce shortly after extraction which limits large-scale production
Solution Approach 1:
The patent applies preliminary action by delivering transient immortalizing factors (such as TERT mRNA, CDK4 mRNA, or small molecule inhibitors) to cells before culturing them at scale. This preliminary treatment temporarily induces an immortalized state, enabling extended proliferation capacity without permanent genetic modification. The factors are removed after the desired proliferation is achieved, allowing cells to return to their natural state while having already accomplished the necessary expansion for cultured meat production.
2Quantity of substance
If repeated satellite cell isolations are performed to generate large amounts of biomass, then cell supply increases, but animal use and suffering increase
Solution Approach 1:
The patent enables self-service by allowing a single initial cell isolation to produce sufficient biomass through transient immortalization. Instead of requiring repeated animal interventions, the initially isolated cells are treated with transient immortalizing factors that enable them to self-proliferate extensively in culture. This single isolation event generates enough cells for large-scale cultured meat production, eliminating the need for repeated satellite cell isolations and thereby reducing animal use and suffering while still achieving the required biomass quantity.
3Reliability
If small-scale production processes are used for cultured meat, then cell quality is maintained, but production cost increases and scalability is limited
Solution Approach 1:
The patent applies parameter changes by temporarily altering the cellular state through transient immortalizing factors during the expansion phase. This allows cells to transition from a limited-proliferation state to an extended-proliferation state, enabling large-scale production. After sufficient biomass is generated, the transient factors are removed and cells return to their natural state, ensuring that the final cultured meat product is produced from cells with appropriate quality characteristics. This parameter modulation enables both scalability and maintenance of cell quality.
Data Source
AI summary
The present disclosure relates to cultured tissue, methods for production of the cultured tissue, e.g., cultured meat, that is not genetically modified. Further, the disclosure provides method of temporary immortalization of cells for propagation in vitro.