1. A composition for delivering an agent to a cell, comprising:
a bispecific affinity reagent, comprising a first affinity reagent covalently linked to a second affinity reagent, wherein the first affinity reagent binds to a molecule on the surface of a cell, and the second affinity reagent binds to an intracellular target, and
wherein the bispecific affinity reagent comprises an antibody, antibody fragment, antibody-like molecule, a single protein, or a specific scFv; and
a pH-responsive, membrane destabilizing polymer.
2. The composition of claim 1, wherein the first affinity reagent and the second affinity reagent are included in a single polypeptide chain.
3. A composition for delivering an agent to a cell, comprising:
a bispecific affinity reagent, comprising a first affinity reagent covalently linked to a second affinity reagent, wherein the first affinity reagent binds to a molecule on the surface of a cell, and the second affinity reagent binds to an intracellular target, and
wherein the first affinity reagent is an antibody, antibody fragment, antibody-like molecule, a single protein, peptide, oligosaccharide, or aptamer; and
a pH-responsive, membrane destabilizing polymer.
4. The composition of claim 3 wherein the first affinity reagent is a small molecule selected from the group consisting of folate or a ligand for the asialoglycoprotein receptor.
5. The composition of claim 3, wherein the peptide is an RGD peptide.
6. The composition of claim 1, wherein the first affinity reagent comprises a protein transduction domain.
7. The composition of claim 6, wherein the protein transduction domain comprises antennapedia, TAT, VP22, transportan, penetratin, polyarginine, fragments thereof, or combinations thereof.
8. A composition for delivering an agent to a cell, comprising:
a bispecific affinity reagent, comprising a first affinity reagent covalently linked to a second affinity reagent, wherein the first affinity reagent binds to a molecule on the surface of a cell, and the second affinity reagent binds to an intracellular target, and
wherein the second affinity reagent is an antibody, antibody fragment, antibody-like molecule, peptide, or aptamer; and
a pH-responsive, membrane destabilizing polymer.
9. The composition of claim 8, wherein the peptide is BH3 or BAK-BH3.
10. A composition for delivering an agent to a cell, comprising:
a bispecific affinity reagent, comprising a first affinity reagent covalently linked to a second affinity reagent, wherein the first affinity reagent binds to a molecule on the surface of a cell, and the second affinity reagent binds to an intracellular target, and
wherein the intracellular target is a DNA binding protein, a cytoplasmic domain of a membrane receptor, a kinase, a GTPase, a phosphatase, or a protein in the Bel family of proteins; and
a pH-responsive, membrane destabilizing polymer.
11. The composition of claim 10, wherein the DNA binding protein is p53.
12. The composition of claim 10, wherein the GTPase is ras.
13. The composition of claim 10, wherein the polymer is a copolymer comprising:
a membrane destabilizing segment comprising a plurality of anionic species that are anionic at about neutral pH, and a plurality of hydrophobic species, and, optionally a plurality of cationic species that are cationic at about neutral pH.
14. The composition of claim 13, wherein the copolymer further comprises:
an amphiphilic or hydrophilic segment.
15. A composition for delivering an agent to a cell, comprising:
a bispecific affinity reagent, comprising a first affinity reagent covalently linked to a second affinity reagent through a cleavable linker, wherein the first affinity reagent binds to a molecule on the surface of a cell, and the second affinity reagent binds to an intracellular target, and
a pH-responsive, membrane destabilizing polymer.
16. A composition for delivering an agent to a cell, comprising:
a bispecific affinity reagent, comprising a first affinity reagent covalently linked to a second affinity reagent, wherein the first affinity reagent binds to a molecule on the surface of a cell, and the second affinity reagent binds to an intracellular target, and
a pH-responsive, membrane destabilizing polymer, wherein the pH-responsive, membrane destabilizing polymer comprises a plurality of pendant linking groups, wherein the first affinity reagent is linked to the polymer and wherein the second affinity reagent is linked to the polymer.
17. The composition of claim 16, wherein the first affinity reagent is linked to an end group of the polymer.
18. The composition of claim 16, wherein the second affinity reagent is linked to one of the plurality of pendant linking groups.
19. The composition of claim 16, further comprising a plurality of second affinity reagents, wherein the plurality of second affinity reagents is linked to the polymer via the pendant linking groups.
20. The composition of claim 16, further comprising a plurality of first affinity reagents, wherein the plurality of first affinity reagents is linked to the polymer via the pendant linking groups.
21. The composition of claim 1, further comprising a therapeutic or diagnostic agent.
22. The composition claim 16, wherein the second affinity reagent is cleavably linked to the polymer.
23. The composition of claim 16, wherein the second affinity reagent is an antibody, antibody fragment, antibody-like molecule, or peptide.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. Flexible electric line comprising:
at least one electrical conductor, having a high tensile, nonmetallic element and a plurality of highly conductive metal wires arranged around it;
wherein said high tensile element is a loose composite of a large number of aramid fibers, said loose composite of a large number of aramid fibers being easily deformable when said at least one conductor is to be attached by crimping to contact parts;
wherein the cross section of said high tensile element is the same as that of one of the metallic wires; and
said conductor surrounded by a layer of insulation.
2. The flexible electric line according to claim 1, wherein the aramid fibers are coated with a moisture-repellent material.
3. The flexible electric line according to claim 2, wherein the wires are made of copper.
4. The flexible electric line according to claim 2, wherein said moisture-repellent material is either one of resin and wax.
5. The flexible electric line according to claim 1, wherein the wires are made of copper.