Polypeptide Display on Intracellular Tubular Structures
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Solution Overview
Problem
The mechanisms of Type VI secretion systems (T6SS) in bacteria, particularly how they transport toxic proteins across cell membranes, are not well understood, and existing methods do not effectively display polypeptides in a form that enhances immunogenicity for vaccine production.
Innovation Solution
Methods and compositions for displaying a polypeptide on a tubular structure formed by culturing bacterial cells expressing a construct encoding a polypeptide fused to an intracellular tubular protein, such as VipA or VipB, allowing the formation of an intracellular tubular structure that displays the polypeptide, which can be used to produce antibodies or vaccines.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If polypeptides are displayed on tubular structures formed by intracellular tubular proteins (VipA/VipB), then immunogenicity is enhanced and immune response is improved, but the complexity of the production system increases due to requiring bacterial cell culture and tubular structure formation
Solution Approach 1:
The patent uses intracellular tubular proteins (VipA/VipB) as intermediary structures to display polypeptides. These tubular proteins naturally form organized structures within bacterial cells and serve as a platform to present the polypeptide of interest, thereby enhancing immunogenicity without requiring complex external display systems.
Solution Approach 2:
The bacterial cell system is leveraged to automatically perform the functions of tubular structure formation and polypeptide display. By expressing the polypeptide fused to or associated with intracellular tubular proteins, the system self-organizes the display structure through natural protein-protein interactions, eliminating the need for manual assembly or complex external scaffolding.
2Manufacturing precision
If polypeptides are fused to intracellular tubular proteins for display, then the polypeptide conformation is maintained similar to native protein, but the ease of manufacture decreases due to requiring specific bacterial expression systems
Solution Approach 1:
The patent utilizes changes in the physical and chemical environment within bacterial cells (such as molecular chaperones, folding conditions, and cellular redox state) to ensure proper polypeptide conformation. By harnessing the native cellular environment, the system maintains polypeptide structure similar to native protein without requiring complex external folding conditions.
3Reliability
If tubular structures are formed intracellularly to display polypeptides, then vaccine efficacy is enhanced, but the loss of time increases due to requiring bacterial cell culture and structure formation processes
Solution Approach 1:
The patent employs preliminary action by using bacterial cell systems that are already equipped with the machinery to form tubular structures and express proteins. The bacterial cells are pre-programmed with the genetic constructs encoding the polypeptide-tubular protein complexes, allowing rapid assembly of display structures once induced, thereby reducing overall production time.
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 displayed polypeptides maintain a conformation similar to the native protein and are more immunogenic, facilitating enhanced immune responses and vaccine efficacy.
Implementation Method 1
culturing a bacterial cell that expresses a first intracellular tubular protein, and that comprises a construct encoding a polypeptide of interest fused to a second intracellular tubular protein, under conditions that permit the expression of said first and second intracellular tubular proteins, wherein such expression permits the formation of an intracellular tubular structure
Data Source
AI summary
Provided herein are methods and compositions for displaying a polypeptide on a tubular structure and uses of such displayed polypeptides in the production of antibodies or vaccines.