Receptor-mediated gene delivery using bacteriophage vectors
Filamentous phage particles displaying a ligand on their surface are used to deliver a therapeutic gene to a cell. The ligand is a fusion protein with a phage capsid protein, covalently conjugated to phage particles, or complexed with modified phage particles.
1. 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.
2. The method according to claim 1 , wherein the ligand is an antibody.
3. The method according to claim 2 , wherein the antibody is a single-chain antibody.
4. The method according to claim 2 , wherein the antibody reacts with HER2/neu.
5. The method according to claim 1 , wherein the ligand is genetically fused with a phage capsid protein.
6. The method according to claim 5 , wherein the phage capsid protein is gene III.
7. The method according to claim 5 , wherein the phage capsid protein is gene VIII.
8. The method according to claim 1 , wherein the ligand is chemically conjugated to a phage capsid protein.
9. The method according to claim 1 , wherein the phage genome is a phagemid.
10. The method according to claim 1 , wherein the phage genome is a hybrid vector.
11. The method according to claim 1 , wherein the phage particles display a nuclear localization sequence on the surface of the phages.
12. The method according to claim 1 , wherein the vector encodes a gene product selected from the group consisting of protein, ribozyme, and antisense oligonucleotide.