Engineered Bacteriophage Antigen Delivery for Commensal Bacteria
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Solution Overview
Problem
Current strategies for treating or preventing bacterial infections, particularly in the context of growing antibiotic resistance, are inadequate in effectively targeting commensal bacteria without harming them, and existing bacteriophages often fail to induce specific immune responses without affecting the commensal bacteria.
Innovation Solution
Engineered bacteriophages are designed to bind to and insert nucleic acid encoding antigens into commensal bacteria, allowing the expression and release of antigens without causing lysis, thereby priming an immune response against infectious agents without affecting the commensal bacteria.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If bacteriophages are used to target commensal bacteria, then immune response against pathogens is induced, but commensal bacteria are harmed or killed
Solution Approach 1:
The patent extracts the harmful lytic cycle components from the bacteriophage while retaining the beneficial gene delivery capability. The engineered phage removes genes encoding lytic enzymes and structural proteins, keeping only the nucleic acid injection function to deliver antigen-encoding genes into commensal bacteria without causing lysis.
Solution Approach 2:
Instead of using bacteriophages to kill pathogens directly (conventional approach), the patent inverts the strategy by using engineered phages to deliver protective antigens through commensal bacteria, transforming the commensal bacteria into antigen factories that prime immune responses without direct phage-pathogen interaction.
2Reliability
If bacteriophages are engineered to express antigens, then specific immune response is primed, but the bacteriophage cannot produce progeny
Solution Approach 1:
The patent extracts and removes genes encoding viral structural proteins, replication enzymes, and lytic functions from the bacteriophage genome, retaining only the essential nucleic acid injection machinery and antigen-encoding genes for immunogenicity without compromising the inability to produce progeny.
Solution Approach 2:
The patent performs preliminary genetic engineering to insert antigen-encoding genes into the phage genome before infection, ensuring that antigens are expressed and presented to the immune system in advance, while the phage remains incapable of replication or progeny production.
3Quantity of substance
If bacteriophages insert nucleic acid into commensal bacteria, then antigen expression occurs, but the commensal bacterium is lysed
Solution Approach 1:
The patent extracts and eliminates genes encoding lytic enzymes and structural proteins from the engineered bacteriophage, retaining only the nucleic acid injection function. This allows the phage to deliver antigen-encoding genes into commensal bacteria without triggering lysis or cell death.
Solution Approach 2:
The patent uses the commensal bacterium as an intermediary host cell that expresses the inserted antigen genes and releases the antigen into the environment without being destroyed. The commensal bacterium serves as a temporary factory for antigen production, avoiding direct harmful interaction between the phage and the bacterium.
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
This approach enables the induction of a specific immune response against pathogens while maintaining the health of commensal bacteria, providing a prophylactic and therapeutic solution for infectious diseases and potentially cancer.
Implementation Method 1
a bacteriophage receptor for a commensal bacterium
Implementation Method 2
inserting its genome polynucleotide into the commensal bacterium
Implementation Method 3
the heterologous antigen gene optionally comprises a signal sequence capable of driving release of the heterologous antigen from the commensal bacterium
Data Source
AI summary
The present invention discloses an engineered bacteriophage capable of binding to a commensal bacterium and inserting its genome polynucleotide into the commensal bacterium, but incapable of producing progeny, incapable of carrying out a lysogenic cycle and incapable of carrying out a lytic cycle within the commensal bacterium, wherein the engineered bacteriophage comprises a genome polynucleotide including at least one gene encoding at least one heterologous antigen(s) under the control of a promoter.