Synthetic mimics of mammalian cell surface receptors: method and compositions
The present invention relates to new synthetic receptors. More particularly, the present invention relates to the use of the synthetic receptors for delivering a protein, peptide, drug, prodrug, lipid, nucleic acid, carbohydrate or small molecule into a target cell via receptor-mediated endocytosis. According to the invention, novel synthetic mimics of cell surface receptors have been designed and methods for use of the same are disclosed.
1. A method of producing a therapeutic effect by delivering a synthetic cell receptor into a cell comprising:
contacting said cell with a synthetic cell receptor that inserts into a cell plasma membrane on a cell surface wherein said receptor comprises:
a target-binding motif, wherein said target-binding motif binds or is covalently linked to a target;
a linker region linking a membrane-binding element with the target-binding motif, wherein said membrane-binding element anchors said receptor into a cell plasma membrane and is a derivative of 3β-cholesterylamine or 3β-dihydrocholesterylamine;
triggering receptor-mediated endocytosis of said receptor;
delivery of said receptor to said cell by an endosome; and
disrupting said endosome by an endosome disrupter to release said target and produce said therapeutic effect.
2. The method of claim 1 further comprising the recycling of said receptor to said cell surface.
3. The method of claim 1 wherein said cells are infected with a pathogen that secretes membrane-disruptive proteins.
4. The method of claim 3 wherein said pathogen is bacterial, viral or a microorganism.
5. The method of claim 1 wherein said target is a member selected from the group consisting of a protein, polypeptide, peptide, antibody, ligand, cytokine, growth factor, immunoglobulin, nucleic acid, lipid, carbohydrate, membrane, prodrug, drug, small molecule or a fragment thereof and combinations of the same.
6. The method of claim 1 wherein said endosome disruptor is a member selected from the group consisting of a peptide, protein, nucleic acid, lipid, polymer, or small molecule, an immunoglobulin or a fragment thereof, hemagglutinin or a fragment or variant thereof, listeriolysin O, GALA, endoporter, poly(alkylacrylic acid) and combinations of the same.
7. The method of claim 1 wherein said endosome disruptor is a small molecule or macromolecule that preferentially disrupts membranes at acidic (endosomal) pH (pH≦7).
8. The method of claim 1 wherein said therapeutic effect is bacteriocidal, bacteriostatic, anticancer, antiviral, or any other biological response.