In alternative embodiments, provided are compositions, products of manufacture and methods for treating, ameliorating and preventing infections, disorders and conditions in animals including: delivering a (i) bacteriophage (ii) prophage, the phagemid or phage-like particle, (iii) general transducing agent (GTA), or small, tailed bacteriophage-like particle, (iv) Metamorphosis Associated Contractile structure (MACs) or (v) phage-derived product into a tissue, or the blood stream or lymphatic system of the animal, e.g., the mammal; or delivering to a tissue or organ of the animal; or treating a bacterial or viral infection in the animal; generating an immune response in the animal; or treating a disease or condition in an individual in need thereof; or delivering a payload or a composition, e.g., in vivo, to the animal, or labelling, tagging or coating a cell in vivo in the animal.

A modified bacteriophage capable of infecting a plurality of different target bacteria, which bacteriophage includes a toxin gene encoding a toxin protein which is toxic to the target bacteria; wherein the bacteriophage is lytic; and wherein the bacteriophage expresses host range determinant proteins which have a plurality of bacterial host specificities.

The present invention provides methods and compositions for maintaining and improving the integrity of gastrointestinal epithelial tight junctions, thereby helping to maintain healthy paracellular permeability of the GI epithelium. The present invention provides methods and compositions for the treatment or prevention of various conditions that are associated with gastrointestinal paracellular permeability, including various autoimmune conditions, inflammatory liver diseases, as well as inflammatory conditions of the large or small intestines.

The present disclosure provides compositions including recombinant B11 bacteriophages, methods for making the same, and uses thereof. The recombinant B11 bacteriophages disclosed herein are useful for the identification and/or antibiotic susceptibility profiling of specific bacterial strains/species present in a sample.

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

The present disclosure relates generally to methods and compositions for transferring a genetic circuit from one prokaryotic cell (donor cell) to another prokaryotic cell (recipient cell or target cell which are used interchangeably herein). More specifically, the present disclosure relates to prokaryotic donor cells comprising (i) a genetic circuit of interest and (ii) one or more expressed transcriptional repressor proteins and the use of said donor cells in the efficient transfer of the genetic circuit into a prokaryotic recipient cell. The genetic circuit includes nucleic acid sequences encoding a RNA molecule or protein of interest.

The present invention provides a recombinantly modified PEGylated bacteriophage expressing a mammalian antigen presenting cell chemoattractant. The present invention further provides methods of treatment of mammalian subjects having a bacterial infection by the administration of a pharmaceutically acceptable formulation of a recombinantly modified PEGylated bacteriophage expressing a mammalian antigen presenting cell chemoattractant. The present invention further provides pharmaceutically acceptable formulations of recombinantly modified PEGylated bacteriophage expressing a mammalian antigen presenting cell chemoattractant. The present invention further provides a method of inducing an antibacterial immune response in a mammalian subject having bacterial infection by the administration of a pharmaceutically acceptable formulation of a recombinantly modified PEGylated bacteriophage expressing a mammalian antigen presenting cell chemoattractant. The present invention further provides a recombinantly modified PEGylated bacteriophage that avoids neutralization by the Cas9 system. In one embodiment, the present invention further provides a recombinantly modified PEGylated bacteriophage expressing an anti-Cas9 protein. The present invention further provides a recombinantly modified PEGylated bacteriophage the genome of which has been modified to eliminate one or more protospacer adjacent motifs.

Some aspects of the present disclosure provide methods for evolving recombinases to recognize target sequences that differ from the canonical recognition sequences. Some aspects of this disclosure provide evolved recombinases, e.g., recombinases that bind and recombine naturally-occurring target sequences, such as, e.g., target sequences within the human Rosa26 locus. Methods for using such recombinases for genetically engineering nucleic acid molecules in vitro and in vivo are also provided. Some aspects of this disclosure also provide libraries and screening methods for assessing the target site preferences of recombinases, as well as methods for selecting recombinases that bind and recombine a non-canonical target sequence with high specificity.

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.

The present invention concerns a production bacterial cell for producing phage particles or phage-derived delivery vehicles, said production bacterial cell stably comprising at least one phage structural gene(s) and at least one phage DNA packaging gene(s), said phage structural gene(s) and phage DNA packaging gene(s) being derived from a first type of bacteriophage, wherein the expression of at least one of said phage structural gene(s) and/or at least one of said phage DNA packaging gene(s) in said production bacterial cell is controlled by at least one induction mechanism, and wherein said production bacterial cell is from a bacterial species or strain different from the bacterial species or strain from which said first type of bacteriophage comes and/or that said first type of bacteriophage targets.