In certain embodiments, the present invention provides a DNA nanostructure nanorobot comprising: a single stranded DNA scaffold strand of about 5,000 to 10,000 bases in length; a plurality of staple strands of DNA, wherein each staple strands are about 20 to 40 bases in length, wherein each staple strand has a unique sequence and is hybridized to a specific position on the DNA scaffold strand, wherein the plurality of staple strands hybridized to the DNA scaffold form a sheet having a top surface and a bottom surface; and one or more fastener strands of DNA, wherein the one or more fastener strands of DNA is capable of fastening the sheet into an origami structure.

Provided are engineered phages populations, which are homogeneous in length, as well as methods of making and methods of using such phages. Also provided are engineered chlorotoxin -phages as well as their methods of making and using. The disclosed homogeneous phage populations and chlorotoxin-phages may be used, for example, for treating and/or imaging tumors, such as central nervous system tumors.

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.

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.

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

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.

The present invention describes applications and methods (1) to use bacteriophage Cf and its variants to prevent and treat the citrus canker pathogen, Xanthomonas citri subsp. citri; (2) to engineer recombinant Cf phages that the infectivity is controllable without being harmful to the rest of environment; (3) to engineer and produce recombinant Cf phages with longer storage shelf life; (4) to use Cf phage as a vector for the introduction and insertion of foreign genetic material into Xanthomonas citri subsp. citri. genome; (5) to use and engineer Xp12 and Xf bacteriophages to inhibit Xanthomonas oryzae pv. oryzae, the causal agent of the rice blight disease.

The invention relates to a filamentous bacteriophage, carrying bacterial Lipopolysaccharide (LPS) endotoxin on its surface, for use in treating cancer and in inhibiting angiogenesis, and in a different context, for use in promoting angiogenesis in diseases or conditions in which there is insufficient angiogenesis.

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 are antibacterial phages that selectively kill bacteria having a drug resistance gene or the like. Antibacterial phage for this includes CRISPR-Cas13a with a target sequence that recognizes a specific gene as a target. This target sequence is designed as a spacer sequence for crRNA of 14-28 bases. Specific genes are drug resistance genes and toxins. The drug resistance genes are included in bacterial genomes and/or plasmids having one or any combination of the group including: methicillin-resistant Staphylococcus aureus, vancomycin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, penicillin-resistant pneumococcus, multidrug-resistant Pseudomonas aeruginosa, multidrug-resistant Pseudomonas aeruginosa, carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant cephalosporins, third-generation cephalosporin-resistant Pseudomonas aeruginosa, third-generation cephalosporin-resistant E. coli, and fluoroquinolone-resistant E. coli.