Monocyte-specific particulate delivery vehicle
View Patent ↗The inventive vector specifically directs entry into a cell of monocytic origin. The vector is composed of a nucleic acid component, a lysosome evading component and a particle that can be phagocytized. The vector itself, or cells pretreated with the vector, are useful in all gene medicine applications. Because it is specific for monocytic cells, the inventive vector is particularly suited to vaccine applications. Due to the ability of monocytic cells to target tumors, the inventive vector also is suitable for use in anti-tumor applications, including conventional gene therapy.
1. A composition for directed entry into a monocyte cell comprising (i) nucleic acid encoding a protein (ii) a lysosome evading component and (iii) a bead vector particle that can be phagocytized, wherein said lysosome evading component is a non-infectious virus or non-infectious component of a virus.
2. The composition of claim 1 wherein said nucleic acid is selected from the group consisting of DNA and RNA.
3. The composition of claim 1 wherein said nucleic acid is encoded in an expression vector.
4. The composition of claim 3 wherein said expression vector contains a nuclear promoter.
5. The composition of claim 4 wherein said promoter is a CMV promoter.
6. The composition of claim 1 , wherein said virus is adenovirus.
7. The composition of claim 1 further comprising a nucleic acid protecting component.
8. The composition of claim 7 wherein said component is selected from the group consisting of protamine, polyarginine, polylysine, histone, histone-like proteins, synthetic polycationic polymers and a core particle of a retrovirus with the appropriate packaging sequence included in the RNA sequence.
9. The composition of claim 1 wherein said nucleic acid and said lysosome evading component are attached to the particle by antibody attachment.
10. The composition of claim 1 wherein said nucleic acid and said lysosome evading component are attached to the particle by interaction between avidin and biotin.
11. The composition of claim 1 further comprising a multiple binding vehicle that binds the nucleic acid.
12. The composition of claim 1 wherein said lysosome evading component is the adenovirus penton protein.
13. The composition of claim 1 , wherein said non-infectious virus or non-infectious component of a virus is non-replicative.
14. The composition of claim 1 , wherein said composition is a pharmaceutical composition that comprises a pharmaceutically suitable excipient.
15. The composition of claim 14 , wherein said non-infectious virus or non-infectious component of a virus is non-replicative.
16. The pharmaceutical composition of claim 14 , wherein said protein is an antigen.
17. The composition of claim 1 , wherein said protein is an antigen.
18. A composition for directed entry into a monocyte cell comprising (i) nucleic acid encoding a protein, (ii) a lysosome evading component and (iii) a bead vector particle that can be phagocytized, wherein said lysosome evading component is a biomimetic polymer.
19. The composition of claim 18 , wherein said protein is an antigen.
20. The composition of claim 18 , wherein said composition is a pharmaceutical composition that comprises a pharmaceutically suitable excipient.
21. A composition for directed entry into a monocyte cell comprising (i) nucleic acid encoding a protein (ii) a lysosome evading component and (iii) a bead vector particle that can be phagocytized, wherein said lysosome evading component is a non-infectious virus.
22. A composition for directed entry into a monocyte cell comprising (i) nucleic acid encoding a protein (ii) a lysosome evading component and (iii) a bead vector particle that can be phagocytized, wherein said lysosome evading component is a non-infectious component of a virus.
23. A composition for directed entry into a monocyte cell comprising (i) nucleic acid encoding a protein (ii) a lysosome evading component and (iii) a bead vector particle that is about 0.5 to about 2.5 microns and allows the composition to be phagocytized by monocytic cells, and wherein the lysosome evading component is a non-infectious virus or non-infectious component of a virus.