An engineered phage-derived particle (PDP) for expressing a transgene in a target cell transduced with a bacteriophage, the PDP includes (i) less than about 500 bp of DNA from the bacteriophage genome, (ii) an ITR-flanked therapeutic gene up to 20 kb, (iii) an endosomal escape sequence, (iv) a nuclear localization sequence, and (v) a cell-specific targeting moiety. The PDP may escape lysosomal degradation, traffic across the nuclear envelope and expressed a therapeutic gene in a mammalian cell.

Antibodies binding to human claudin 18.2 (CLDN 18.2) and bispecific antibodies binding to both human CLDN 18.2 and PD-L1, pharmaceutical compositions comprising such, and methods of using such for treating target diseases such as cancer.

Disclosed here are phage compositions comprising Type I CRISPR-Cas systems and methods of use thereof. In some embodiments, disclosed herein is a nucleic acid sequence comprising (a) a first CRISPR array designed to be operable with a first Type I CRISPR-Cas system, and (b) a second CRISPR array designed to be operable with a second Type I CRISPR-Cas system, wherein the first Type I CRISPR-Cas system and the second Type I CRISPR-Cas system are different Type I CRISPR-Cas systems.

Provided are amino acid sequences capable of binding to and inhibiting a Cas protein's ability to bind to a nucleic acid molecule, thereby inhibiting the Cas protein's function in genome editing. Such Cas protein inhibitors, which can be comprised of a major coat protein (G8P), an extracellular region of the G8P (G8P.sub.EX), or a biological equivalent, are useful in improving the specificity of Cas protein-based genome editing procedures.

The present invention provides a gene including an M13 p5 expressing cassette, which includes a promoter, a ribosome binding site (RBS) and a protein 5 (p5) coding region, wherein at least one base of sequences between the RBS and the p5 coding region is mutated. Using this gene may increase production of single-stranded DNA.

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.

Provided herein, in some embodiments, are engineered phagemids that comprise at least one synthetic genetic circuit, wherein the at least one synthetic genetic circuit comprises gene sequences encoding at least one non-lytic antimicrobial peptides (AMPs) and/or antibacterial toxin proteins, a stable origin of replication, and a bacteriophage-packaging signal, wherein the engineered phagemid does not comprise some or all gene sequences encoding bacteriophage proteins required for assembly of a bacteriophage particle.

A combined Kunkel mutagenesis and phage-display method for producing bivalent binding agents is provided.

The present disclosure provides materials and methods for selectively engineering at least one bacterial strain among a mixed population of bacterial strains in the gut of a subject. In some embodiments, a bacteriophage comprising at least one nucleic acid is administered which selectively infects a bacterial strain under conditions that allow expression of the nucleic acid. The present disclosure thus provides compositions and methods for precisely modifying or reducing a population of bacteria in a mixed population in the gut microbiome.

Embodiments of the invention are generally directed to compositions and methods of delivering one or more transgene to a target cell, such as a tumor cell, in a site-specific manner to achieve enhanced expression and to constructs and compositions useful in such applications. In certain aspects, expression from a therapeutic nucleic acid may be assessed prior to administration of a treatment or diagnostic procedure to or on a subject.