Disclosed herein are methods, compositions, kits, and systems for rapid multiplex detection of a microorganism of interest. Recombinant bacteriophages encoding capture moiety-indicator protein fusion products allow for the capture of indicator proteins on a surface. Cocktail compositions of recombinant bacteriophages can be used to detect potentially harmful bacteria. The specificity of recombinant bacteriophages for binding microorganisms allows targeted and highly specific detection of a microorganism of interest.

The invention provides hybrid and recombinant phagemid vectors for expressing a transgene in a target cell transduced with the vector. A recombinant phagemid particle comprises at least one transgene expression cassette which encodes an agent which exerts a biological effect on the target cell, characterised in that the phagemid particle comprises a genome which lacks at least 50% of its bacteriophage genome. The invention extends to the use of such phagemid expression systems as a research tool, and for the delivery of transgenes in a variety of gene therapy applications, DNA and/or peptide vaccine delivery and imaging techniques. The invention extends to in vitro, in vivo or in situ methods for producing viral vectors, such as recombinant adeno-associated viruses (rAAV) or lentivirus vectors (rLV), and to genetic constructs used in such methods.

Compositions, systems and methods of improving the health of the microbiome of an individual's skin relate to the provision of skin contacting formulations containing beneficial bacteria and other microbe components to foster the growth and maintenance of a healthy skin microbiome. A topical application of Lactobacillus crispatus is employed to ameliorate skin barrier damage and inflammation using unique combinations of probiotics, prebiotics, and other skin-beneficial ingredients, effectively treating inflammatory skin diseases, such as atopic dermatitis, psoriasis and acne. The topical application of Lactobacillus crispatus to an individual's skin reduces inflammation through the production of tryptophan metabolites that act as AHR agonists.

A method for reducing the population of at least one adipogenic bacteria species, the method comprising the following steps: a) providing a biologic sample which comprises at least one adipogenic bacteria species; and b) providing bacteriophages of at least one bacteriophage species which are specific to at least one adipogenic bacteria species and comprise at least one nucleic acid functionally bound to a promoter and/or to a regulatory element; and c) exposing the biologic sample to and incubating it with the bacteriophages, incubation taking place until the population of the adiopogenic bacteria species has been reduced by at least 70%; as well as relating to bacteriophages and their use.

Provided herein are methods and compositions for killing a target bacterium. Also disclosed are engineered bacteriophages.

The methods described herein are for treating infections in individuals having cancer and who are receiving cancer immunotherapy, preferably employing a CRISPR system to selectively kill or reduce the numbers of pathogenic bacteria within the individual and thereafter, administering an immune checkpoint inhibitor thereto. In particular embodiments, the pathogenic bacteria is one of E. coli, Pseudomonas aeruginosa, Klebsiella bacteria, Staphylococcus aureus; Streptoccocus; Salmonella; Shigella; Mycobacterium tuberculosis; Enterococcus; Clostridium; Neisseria gonnorrhoea; Acinetobacter baumannii; and Campylobacter bacteria and the checkpoint inhibitor is selected from the group consisting of nivolumab, pembrolizumab, pidilizumab, AMP-224, AMP-514, STI-A1110, TSR-042, RG-7446, BMS-936559, MEDI-4736, MSB-0020718C, AUR-012 and STI-A1010. Further embodiments include enhancing the growth of a second bacteria in the individual, such bacteria including Akkermansia, Bacteroides, Bifidobacterium, Enterococcus, Fusobacterium, Coprococcus, LactoBacillus, Propionibacterium, Ruminococcus, Veillonella, Prevotella, and F. prausnitzii. The CRISPR system may include Cas9, Cpf1 and Cas3, and may be delivered using a bacteriophage.

The present invention is related to the field of CRISPR-Cas9 gene editing platforms. In particular, the present invention has identified Type II-C Cas9 anti-CRISPR (Acr) inhibitors that control Cas9 gene editing activity. Co-administration of such Acr inhibitors may provide an advantageous adjunct in permitting safe and practical biological therapeutics through spatial or temporal control of Cas9 activity; controlling Cas9-based gene drives in wild populations to reduce the ecological consequences of such forced inheritance schemes; and contributing to general research into various biotechnological, agricultural, and medical applications of gene editing technologies.

Modified bacteriophage, uses thereof, and compositions containing the modified bacteriophage are described. The compositions are useful for human treatment and may treat various conditions, including bacterial infections.

A method for modifying the genome of a target phage is described. Compositions comprising such modified phage are also described. The compositions may be formulated as a medicament, which are useful for human treatment and may treat various conditions, including bacterial infections.

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.