Receptor-mediated gene delivery using bacteriophage vectors

DETAILED DESCRIPTION In one aspect, the invention provides a method of gene delivery, comprising: contacting a mammalian cell with filamentous phage particles presenting a ligand on their surfaces, wherein a vector within the phage encodes a gene product under control of a promoter.
In related aspects, the invention provides methods of treating tumors, smooth muscle cell diseases, or angiogenic diseases, comprising administering a pharmaceutical composition to a patient comprising a physiologically acceptable buffer and filamentous phage particles presenting a ligand on their surfaces, wherein the phage genome encodes a therapeutic gene product under control of a promoter.
In a preferred embodiment, the ligand is a polypeptide reactive with FGF receptor, and in a most preferred embodiment the ligand is FGF-2.
In other embodiments, the ligand is an antibody and preferably a single-chain antibody.
The ligand may be genetically fused with a phage capsid protein or chemically conjugated to form a covalent attachment or by sandwich method.
Generally, the capsid protein for gene fusion is gene III or gene VIII.
In a preferred embodiment, an endosomal escape moiety is incorporated into the ligand or displayed by other means on the surface of the phages.
The ligand or phage may also further comprise a nuclear localization sequence.
In another preferred embodiment, the phage genome is a phagemid.
In preferred embodiments, the therapeutic gene product is selected from the group consisting of protein, ribozyme, and antisense oligonucleotide, and in other embodiments the therapeutic gene product is a cytotoxic agent (e.
g.
, ribosome inactivating protein, such as saporin) or is an antibody that binds to HER2/neu.
In other aspects, the invention provides a pharmaceutical composition comprising a physiologically acceptable buffer and filamentous phage particles presenting a ligand on their surfaces, wherein the phage genome encodes a therapeutic gene product under control of a promoter and filamentous phage particles presenting a ligand on their surfaces, wherein the phage genome encodes a therapeutic gene product under control of a promoter