Propagator Cells Using Host Receptors for High-Titer Phage
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Solution Overview
Problem
Current methods for commercial-scale production of bacteriophages for therapeutic use face challenges with low titer levels and high volume requirements, limiting their effectiveness and scalability.
Innovation Solution
A method and cell system for propagating bacteriophages using propagator cells that express receptors different from the target host, allowing for high-yield production of phages capable of infecting specific bacterial strains.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If standard bacterial culture techniques are used to propagate phage in the target host cells, then the phage can be produced in the cognate host cell, but the production volume becomes unmanageably large and the titer remains low
Solution Approach 1:
The patent introduces a propagator cell as an intermediary host that expresses the target host's cell surface receptor. This mediator allows the phage to be propagated in a surrogate host (the propagator cell) rather than directly in the target host cells, enabling high-titer production in a controlled, smaller volume while maintaining phage specificity for the original target host
Solution Approach 2:
The invention changes the host cell parameter from the target host cell to a propagator cell that expresses the same receptor. This parameter change enables phage propagation in a different bacterial species or strain that is more suitable for scalable production, achieving high titers (10^12 pfu/ml) without requiring unmanageably large volumes
2Quantity of substance
If phage are propagated in large volumes to achieve desirable titer, then the titer requirement can be met, but the manufacturing complexity and scalability are limited
Solution Approach 1:
By using propagator cells as intermediaries, the system achieves high-titer phage production without requiring large-scale culture systems. The propagator cell serves as a bridge that enables concentrated phage production in smaller, more manageable volumes, simplifying the manufacturing process and improving scalability
3Quantity of substance
If the propagator cell is engineered to express the target host receptor, then high-titer phage production is achieved, but the device complexity increases
Solution Approach 1:
The propagator cell is engineered to express the target host's cell surface receptor, giving it the universal ability to serve both as a surrogate host for phage propagation and as a model for studying host-phage interactions. This multi-functionality justifies the engineering complexity by enabling high-titer production while maintaining relevance to the original target host
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
Enables high-titer production of bacteriophages suitable for therapeutic applications, reducing manufacturing volume and enhancing scalability.
Implementation Method 1
The adsorption of bacteriophages onto host cells is, in all but a few rare cases, a sine qua non condition for the onset of the infection process
Data Source
AI summary
The invention provides propagator cells and methods for propagating phage and transduction particles.