Engineered Bacteriophage Vectors for Broad Host Range Delivery
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Solution Overview
Problem
Current treatments for bacterial infections, particularly those caused by antibiotic-resistant bacteria, face challenges due to the narrow spectrum of bacteriophage activity and the difficulty in broadening the host range of phages, leading to limited effectiveness and potential disruption of the microbiome.
Innovation Solution
Designing bacteriophages or phagemids with a reduced number of restriction sites to enhance DNA delivery efficiency, allowing them to target a broader range of bacterial strains without impairing the microbiome diversity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If bacteriophages are used to treat bacterial infections, then antibiotic-resistant bacteria can be targeted, but the host range of phages is limited and difficult to broaden
Solution Approach 1:
The patent modifies the phage genome by changing parameters such as removing restriction sites and modifying tail fiber proteins to broaden the host range. This allows a single phage to infect multiple bacterial strains while maintaining effective lysis, resolving the contradiction between limited host range and treatment effectiveness.
Solution Approach 2:
The patent employs a modular approach by separating the phage into functional components: tail fiber proteins for host recognition, capsid for DNA packaging, and genome for replication. This segmentation allows independent optimization of each component to achieve both broad host range and reliable infection.
2Adaptability or versatility
If a phage cocktail is used to broaden spectrum coverage, then multiple bacterial strains can be targeted, but regulatory approval becomes difficult
Solution Approach 1:
The patent creates a universal phage platform that can be engineered to target multiple bacterial strains through modifications in tail fiber proteins and genome sequences. This single multi-functional phage replaces the need for multiple specialized phages in a cocktail, simplifying regulatory approval while maintaining broad spectrum coverage.
3Adaptability or versatility
If mutation/selection cycles are used to broaden phage host range, then new bacterial strains can be infected, but the process is time-consuming and mutational spectrum is limited
Solution Approach 1:
The patent performs preliminary engineering of the phage genome in the laboratory before application, pre-modifying tail fiber proteins and removing restriction sites to achieve broad host range. This eliminates the need for time-consuming in-vivo selection cycles, as the desired phage variants are prepared in advance through rational design.
4Adaptability or versatility
If tail fiber swapping is used to broaden host range, then recognition characteristics can be exchanged, but success is limited
Solution Approach 1:
The patent creates composite phage particles by combining engineered tail fiber proteins with modified capsids and genomes. This composite approach ensures that all components work together synergistically to achieve both broad host range and reliable infection, overcoming the limitations of simple tail fiber swapping.
Data Source
AI summary
The present invention relates to a vector, preferably included in a delivery vehicle, comprising no more than 100, preferably no more than 10, restriction sites recognized by the restriction enzymes encoded by each bacterium of a group of bacteria of interest. The invention also relates to the use of said vector, preferably included in a delivery vehicle, as a drug, especially in the treatment of a disease in a patient in need thereof.