Bacteriophage Host Recognition Elements for Extended DNA Transduction
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Solution Overview
Problem
Current bacteriophage-based technologies face limitations in their narrow host range, making it difficult to transduce DNA into restrictive hosts, which hinders advanced genetic manipulations and applications in overcoming antibiotic resistance.
Innovation Solution
A method is developed to prepare and isolate bacteriophages with extended host recognition elements by using defective nucleic acid sequences and packaging signals, allowing for the selection and characterization of compatible host recognition elements, enabling DNA transduction into new hosts without requiring phage propagation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If bacteriophages are used for DNA transduction, then genetic manipulation capability is improved, but host range is limited
Solution Approach 1:
The bacteriophage system is segmented into essential components (capsid, packaging machinery) and replaceable components (host recognition elements, tail fibers). This allows independent optimization of host range without compromising transduction efficiency, as the essential transduction functions are preserved while host recognition components are swapped to target new bacterial strains.
Solution Approach 2:
The patent creates a universal bacteriophage platform that can transduce multiple different bacterial hosts by replacing host recognition elements. The core transduction machinery remains universal and functional across different host types, while the recognition elements are customized for specific target hosts, achieving both broad adaptability and reliable transduction.
2Adaptability or versatility
If host recognition elements are modified to expand host range, then adaptability is improved, but phage propagation capability deteriorates
Solution Approach 1:
The patent extracts the host recognition elements (tail fibers, receptor-binding proteins) from the bacteriophage system and replaces them with recognition elements from phages that can infect the target host. This allows the core propagation machinery to remain intact and functional, while only the host-specific recognition components are changed, thus expanding host range without sacrificing propagation capability.
Solution Approach 2:
The patent changes the biochemical parameters of host recognition by substituting amino acid sequences in tail fiber proteins or receptor-binding domains. These parameter changes in the recognition elements allow binding to new host receptors while maintaining the structural and functional integrity of the overall phage particle for efficient propagation.
3Adaptability or versatility
If defective nucleic acid sequences are used in delivery vehicles, then host range extension is enabled, but packaging efficiency is reduced
Solution Approach 1:
The patent performs preliminary packaging of the defective nucleic acid sequences (lacking complete host recognition elements) into bacteriophage particles using the host's own packaging machinery. The defective sequences are packaged in advance, and then the particles are rescued by co-expression of complementary recognition elements, thereby achieving host range extension without compromising packaging efficiency at the critical step.
Data Source
AI summary
The invention relates to platform for of the preparation of improved nucleic acid delivery vehicles, specifically, vehicles having an extended host recognition ability. The invention further provides improved vehicles, compositions and uses thereof.