Cell transport
The invention relates to novel polypeptides for transporting molecules across cell membranes and, particularly but not exclusively, biological membranes; a conjugate comprising at least one of said polypeptides and at least one selected molecule or agent co-joined or conjugated to said polypeptide for the purpose of transporting said molecule or agent across a cell membrane; a method of transporting at least one selected molecule or agent across a cell membrane involving the use of at least one of said polypeptides; a therapeutic comprising at least one of said conjugates; a combination therapeutic comprising at least one of said conjugates and at least one further therapeutic agent; a method of treatment involving the use of at least one of said conjugates or said therapeutics.
1. A cell penetrating peptide (CPP) for transporting a selected molecule or agent across a cellular membrane, wherein the CPP consists of:
i) RRVQIWFQNKRAKVKR (SEQ ID NO: 1); or
ii) a sequence at least 85% homologous to SEQ ID NO: 1.
2. The CPP according to claim 1 , wherein said amino acid sequence of part ii) is at least 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94% 95%, 96%, 97%, 98% or 99% homologous to SEQ ID NO: 1.
3. The CPP according to claim 1 , wherein said membrane is naturally occurring or synthetic.
4. The CPP according to claim 1 , wherein said membrane is a biological membrane.
5. The CPP according to claim 1 , wherein said CPP is co-joined or conjugated to at least one selected molecule or agent for the purpose of transporting said selected molecule or agent across said membrane.
6. The CPP according to claim 5 , wherein said CPP is covalently or non-covalently attached to or associated with said selected molecule or agent.
7. The CPP according to claim 5 , wherein said selected agent is selected from the group consisting of: small molecules, supramolecular particles, peptides, proteins, plasmid deoxyribonucleic acid (DNA), nucleic acids, small interfering ribonucleic acid (siRNA), antisense oligonucleotides, chemical entities, therapeutic drugs, antibodies, organic dyes, fluorescent labels, quantum dots, and nanospheres.
8. The CPP according to claim 5 , wherein said CPP is attached to said selected molecule or agent by in vivo or in vitro recombination.
9. The CPP according to claim 8 , wherein said CPP is attached to said selected molecule or agent by in vitro recombination.
10. The CPP according to claim 5 , wherein said CPP is conjugated to said selected molecule or agent at either its amino or carboxy terminal.
11. The CPP according to claim 5 , wherein said CPP is located distally from said selected molecule or agent due to the presence of at least one further spacer amino acid residue.
12. The CPP according to claim 11 , wherein said CPP is located 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid residues distal from said selected molecule or agent.
13. A method for transporting at least one selected molecule or agent across a cellular membrane, comprising co-joining or conjugating said CPP according to claim 1 to said at least one selected molecule or agent to be transported, and contacting the complex comprising the CPP and the selected molecule or agent with the cellular membrane.
14. A therapeutic comprising at least one CPP according to claim 1 co-joined or conjugated to a selected therapeutic agent.
15. The therapeutic according to claim 14 , wherein said therapeutic is selected from the group consisting of: a small molecule chemical inhibitor or activator, a protein, a supramolecular particle, a peptide, a plasmid DNA, a nucleic acid, siRNA, an antisense oligonucleotide, a chemical entity, a therapeutic drug, and an antibody.
16. A combination therapeutic comprising at least one therapeutic according to claim 14 and at least one further therapeutic agent.
17. A pharmaceutical composition comprising a therapeutic according to claim 14 and a pharmaceutically acceptable carrier.
18. A method for producing the CPP according to claim 1 , the method comprising culturing a host cell transformed with a nucleic acid molecule encoding said CPP, and harvesting said CPP.
19. A pharmaceutical composition comprising a combination therapeutic according to claim 16 and a pharmaceutically acceptable carrier.
20. A cell penetrating peptide (CPP) for transporting a selected molecule or agent across a cellular membrane, wherein the CPP consists of the amino acid sequence of SEQ ID NO: 1.