This invention provides a robust fermentation process for the expression of a capsid protein of a bacteriophage which is forming a VLP by self-assembly, wherein the process is scalable to a commercial production scale and wherein the expression rate of the capsid protein is controlled to obtain improved yield of soluble capsid protein. This is achieved by combining the advantages of fed-batch culture and of lactose induced expression systems with specific process parameters providing improved repression of the promoter during the growth phase and high plasmid retention throughout the process.

The subject matter of the instant invention relates to methods of enhancing harvesting of phages against a targeted host bacteria, as well as methods of identifying phages likely to have an enhanced propensity to infect and kill an infectious pathogenic bacteria in vivo, from samples comprising phages. The invention also relates to phage libraries, pharmaceutical compositions, methods of treatment, and phage-based diagnostic methods and methods of detecting bacteria related thereto.

Described is an “artificial virus” (AV) programmed with biomolecules that can enter human cells and carry out precise human genome modification. The AVs comprise: at least one viral vector, such as bacteriophage T4; at least one therapeutic molecule, such as DNA, RNA, protein and their complex; and a lipid coating. Also described is a method of human genome modification, using such an AV, and a method of program such an AV.

A simple method and kit for preserving clinical specimens and other biological samples, particularly for the purpose of preserving the concentration of bacteriophage and/or bacteria present in a sample, is described. The method involves rapidly lowering the temperature of the sample (e.g. freezing) to a temperature of −50° C. or lower (especially about −78° C.) in the presence of a suitable cryoprotectant (e.g. 20% glycerol). In one application, the method is used with clinical samples (e.g. urine) taken from a patient undergoing phage therapy for a bacterial infection, wherein the method permits the samples to be transported and/or stored following collection such that the viability of any phage and/or bacteria present is maintained while also inhibiting potential interactions between the phage and bacteria. After thawing of the samples, the samples may be analyzed for phage and/or bacterial concentration to provide information on the effectiveness of the phage therapy.

In alternative embodiments, provided are products of manufacture and kits, and methods, to enrich for and/or isolate microbes such as viruses and/or phages capable of targeting, e.g., binding to, targeting, and/or killing or otherwise making non-viable or non-pathogenic, specific or desired microbes such as bacteria. In alternative embodiments, provided are products of manufacture comprising: a virus and/or a phage (a bacteriophage). In alternative embodiments, provided are products of manufacture and kits containing a virus and/or a phage (a bacteriophage) enriched for, selected for or isolated by a method as provided herein, or a microbe containing a virus and/or a phage (a bacteriophage) enriched, selected for and/or isolated by a method as provided herein.

The present invention is directed to a method for producing bacteriophages infecting a bacterial host such as Flavobacterium columnare or Aeromonas sp, the method comprising the steps of adding the bacterium to a sterile culture medium supplemented with mucin or another mucus component, incubating said culture medium, thereby obtaining a bacterial culture, optionally collecting the supernatant containing floating (planktonic) bacterial cells from said culture and transferring the supernatant to a new container in order to discard most of the biofilm and adding a bacteriophage infecting the bacterium to said bacterial culture obtained from a previous step, and incubating the culture until the phage yield increases or peaks. The method can also be used for preparing modified enrichment cultures for optimized phage isolation. Addition of mucin to soft-agar culture medium is proposed as an optimized technique for viral titration. This invention also covers all relevant steps in setting up a phage therapy product: phage production, phage quantification and phage isolation.

The present invention relates to a method for purifying viruses or virus-like particles using a crosslinked cellulose hydrate membrane and to a kit for purifying viruses or virus-like particles and the use thereof.

The present invention provides new bacteriophages, their selection, compositions, cocktails and formulations thereof, and their administration for the prevention of opportunistic infections in livestock, such as Avian Pathogenic E. Coli (APEC) infections in poultry.

Disclosed herein are methods for the production of mutant bacteriophages with altered host range. Additionally, disclosed herein are methods and systems for rapid detection of microorganisms such as Listeria spp. in a sample. A genetically modified bacteriophage is also disclosed which comprises an indicator gene in the late gene region. The specificity of the bacteriophage, such as Listeria-specific bacteriophage, allows detection of a specific microorganism, such as Listeria spp. and an indicator signal may be amplified to optimize assay sensitivity.

Provided is a method and composition using ROS to increase the production of bacteriophage. According to the subject matter, a production amount of bacteriophage is increased several times in the presence of the sublethal concentration of ROS for host bacteria. Therefore, the method and composition of the subject matter can be useful for producing bacteriophage, which is used as an alternative to antibiotics that cause a serious resistance problem.