Provided is a modified bacteriophage capable of infecting a target bacterium, which bacteriophage includes an / small acid-soluble spore protein (SASP) gene encoding a SASP which is toxic to the target bacterium, wherein the SASP gene is under the control of a constitutive promoter which is foreign to the bacteriophage and the SASP gene.

The present invention discloses an engineered bacteriophage capable of binding to a commensal bacterium and inserting its genome polynucleotide into the commensal bacterium, but incapable of producing progeny, incapable of carrying out a lysogenic cycle and incapable of carrying out a lytic cycle within the commensal bacterium, wherein the engineered bacteriophage comprises a genome polynucleotide including at least one gene encoding at least one heterologous antigen(s) under the control of a promoter.

The present invention discloses a recombinant bacteriophage comprising a phage genome polynucleotide including a gene encoding a heterologous antigen protein(s) and a killing gene encoding a protein that is capable of killing a host bacterium. Such a recombinant bacteriophage is designed to prime a subject's immune response and to kill the bacterium that it infects such that the prime and kill bacteriophage provides two lines of protection against infectious disease.

The invention provides manipulated adenovirus, i.e. a viral particle based on a manipulated adenovirus, for use as a medicament, especially for use in the treatment of tumours. The viral particle of the invention has the advantage of having a preference or specificity for tumour cells, yielding a preferred infection of tumour cells. The viral particle is based on adenovirus, especially type C, preferably serotype 2 (Ad2), more preferably serotype 5 (Ad5), in which the native entire fiber protein, and its coding sequence, respectively, is deleted and replaced by a fusion protein providing specificity for cell surface bound polysialic acid.

A eukaryotic expression vector capable of displaying a multi-chain polypeptide on the surface of a host cell is provided, such that the biological activity of the multi-chain polypeptide is exhibited at the surface of the host cell. Such a vector allows for the display of complex biologically active polypeptides, e.g., biologically active multi-chain polypeptides such as immunoglobulin Fab fragments. The present invention describes and enables the successful display of a multi-chain polypeptide on the surface of a eukaryotic host cell. Preferred vectors are described for expressing the chains of a multi-chain polypeptide in a host cell separately and independently (e.g., under separate vector control elements, and/or on separate expression vectors, thus forming a matched vector set). The use of such matched vector sets provides flexibility and versatility in the generation of eukaryotic display libraries, for example the ability to generate and to display multi-chain polypeptides by combining and recombining vectors that express variegations of the individual chains of a multi-chain polypeptide. Entire repertoires of novel chain combinations can be devised using such vector sets.

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.

Compositions for a phage particle are disclosed. The phage particle is non-replicating and includes at least one heterologous nucleic acid sequence that is capable of being expressed in a target bacteria. The expressed heterologous nucleic acid sequence is non-lethal to the target bacteria.

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.

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.

A eukaryotic expression vector capable of displaying a multi-chain polypeptide on the surface of a host cell is provided, such that the biological activity of the multi-chain polypeptide is exhibited at the surface of the host cell. Such a vector allows for the display of complex biologically active polypeptides, e.g., biologically active multi-chain polypeptides such as immunoglobulin Fab fragments. The present invention describes and enables the successful display of a multi-chain polypeptide on the surface of a eukaryotic host cell. Preferred vectors are described for expressing the chains of a multi-chain polypeptide in a host cell separately and independently (e.g., under separate vector control elements, and/or on separate expression vectors, thus forming a matched vector set). The use of such matched vector sets provides flexibility and versatility in the generation of eukaryotic display libraries, for example the ability to generate and to display multi-chain polypeptides by combining and recombining vectors that express variegations of the individual chains of a multi-chain polypeptide. Entire repertoires of novel chain combinations can be devised using such vector sets.