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.

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.

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.

Various aspects and embodiments of the present disclosure are directed to methods and compositions for functionalizing endogenous bacteria in vivo. The methods include delivering to endogenous bacterial cells a recombinant bacteriophage or phagemid that is engineered to contain at least one genetic circuit.

Described herein are hydrogel compositions comprising cross-linked bacteriophages. The hydrogels are typically bioactive, degradable, for example biodegradable, self-healing, fluorescent, for example autofluorescent, and/or birefringent. The hydrogels described herein may be used as therapeutics or diagnostics, as scaffolds for material synthesis, as catalysts, as membranes or filters, or as biosensor substrates, for example.

The present invention relates to pharmaceutical compositions containing lipid-bacteriophage conjugates, wherein the bacteriophage:lipid ratio is in the range of 3:1 to 100:1 and wherein the lipid is an immunologically active lipid and the bacteriophage is a filamentous bacteriophage, and uses thereof. Preferably, the bacteriophage is engineered to stimulate an immune response and/or bind to a target cell.

The present invention relates to a phage or a composition that comprises it, wherein said phage expresses at least one specific recognition element and is furthermore conjugated with at least 300 molecules of a sonosensitiser. The invention further relates to the use of said phage in a sonodynamic therapy.

Disclosed herein are novel synthetic bacteriophages and bacteriophage compositions, methods of production thereof, and therapeutic uses thereof.

Carrier compositions, including human-safe phages, equipped with one or more angiogenin-binding peptides, and optionally with tumor-homing peptides for use in anti-tumor therapies, are described. The angiogenin-binding peptides bind to and inactivate angiogenin molecules thereby blocking their angiogenic activity thus inhibiting angiogenesis in the tissue in which the compositions are localized.

Various aspects and embodiments of the present disclosure are directed to methods and compositions for functionalizing endogenous bacteria in vivo. The methods include delivering to endogenous bacterial cells a recombinant bacteriophage or phagemid that is engineered to contain at least one genetic circuit.