Virus-free virus-like P4-EKORhE transducing particles and n-kill antimicrobial gene therapeutics

This thesis demonstrates several bioproduction methods to produce gene-delivery vehicles and shows how the virology of the P4 and P2 bacteriophages can be harnessed to establish a bioprocess for producing transducing particles at very high yields, avoiding contamination by the natural virus while maintaining the antimicrobial effectiveness of synthetic genetically encoded antimicrobials. The bioengineered P4-EKORhE is showcased as an optimal system for bioproduction which is used as a gene delivery vehicle and the activity of some genetically encoded antimicrobials is tested in vivo in both pure bacterial cultures and in human cell cultures demonstrating its activity and pre-clinical potential.