Engineered Cell Lines for Cultivated Meat Production
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Solution Overview
Problem
Existing fed-batch processes for cultivated meat production are hindered by the accumulation of by-products that adversely affect cell proliferation and viability, particularly at commercial scales, leading to inefficiencies and increased processing times.
Innovation Solution
Genetically modified cell lines, such as those with knocked out LDHA and PDK1 genes, are developed to reduce lactate production, enhancing cell proliferation and viability by shifting metabolism towards oxidative phosphorylation, thereby improving cell density and reducing waste accumulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If fed-batch process is used for cultivated meat production, then cost is reduced compared to continuous process, but by-products accumulate and adversely affect cell proliferation and viability
Solution Approach 1:
The patent modifies cellular metabolic parameters through genetic engineering (knocking out LDHA and PDK1 genes) to change how cells process glucose and produce by-products. This fundamental parameter change in cellular metabolism allows the fed-batch process to maintain high cell viability while reducing harmful by-product accumulation, thus resolving the contradiction between cost-effectiveness and reliability
2Productivity
If fed-batch process is used to achieve high cell densities, then processing time is reduced, but by-product accumulation inhibits cell proliferation
Solution Approach 1:
The patent converts the harmful effect of by-product accumulation into a beneficial outcome by genetically modifying cells to reduce lactate production. The knocked-out LDHA gene prevents lactate formation, while the knocked-out PDK1 gene redirects metabolism toward oxidative phosphorylation. This transforms the原本的 harmful metabolic by-product issue into a benefit where cells can maintain high proliferation rates for extended periods, achieving both high cell density and reduced processing time
3Object-generated harmful factors
If conventional cell lines are used in fed-batch processes, then lactate accumulates and adversely impacts cell growth, but genetic modification can reduce lactate production
Solution Approach 1:
The patent extracts and removes the problematic metabolic pathways by knocking out specific genes (LDHA and PDK1) responsible for lactate production. This selective removal of harmful metabolic functions allows the cell line to operate without accumulating inhibitory by-products, resolving the contradiction between reducing harmful factors and managing cell line complexity through targeted genetic modifications
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 modified cell lines exhibit improved viable cell density, reduced population doubling time, and lower lactate production, facilitating higher cell densities and extended bioreactor run times, making them suitable for commercial-scale cultivated meat production.
Implementation Method 1
Genetically modified cell lines, such as those with knocked out LDHA and PDK1 genes, are developed to reduce lactate production, enhancing cell proliferation and viability by shifting metabolism towards oxidative phosphorylation
Data Source
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AI summary
Cell lines that can be utilized in fed-batch processes are provided. In preferred embodiments, the cell lines have been modified to reduce or eliminate the production of byproduct(s) that adversely impact cell proliferation and/or viability in fed-batch processes. In some embodiments, the cells are modified by inactivating one or more genes that encode for lactate production. Exemplary genes include lactate dehydrogenase A (LDHA) and pyruvate dehydrogenase kinase 1 (PDK1). Also provided are methods of making and using the cells, for example in food products.