Peptide ligands
A peptide consisting of or comprising an amino acid sequence selected from a) PX 1 X 2 X 3 T [SEQ.ID.NO.:1]; b) PSX 4 S [SEQ.ID.NO.:2]; c) QX 5 X 6 X 7 Q [SEQ.ID.NO.:3]; d) SX 8 S [SEQ.ID.NO.:4], in which X 1 , X 2 and X 3 , which may be the same or different, each represents an amino acid residue; X 4 represents an amino acid residue; and X 5 and X 7 , which may be the same or different, each represents an amino acid residue, X 6 represents an amino acid residue having an amide side chain; and X 8 represent an amino acid having an aliphatic side chain, which peptide binds to dendritic cells and also to other types of cells. The peptide may be used a target non-viral and viral vectors to such cells.
1. An isolated polypeptide comprising a sequence selected from the group consisting of PPNTT (SEQ ID NO: 9), STPPNTT (SEQ ID NO: 17), APSNSTA(SEQ ID NO: 15), and SPALKTV (SEQ ID NO: 16), wherein the length of the polypeptide is up to 30 amino acids, the polypeptide is capable of binding to dendritic cells, and the polypeptide is not a full-length naturally-occurring protein.
2. A peptide selected from the group consisting of PALKT (SEQ ID NO: 6), PSNST (SEQ ID NO: 8), PPNTT (SEQ ID NO: 9), STPPNTT (SEQ ID NO: 17), APSNSTA (SEQ ID NO: 15), and SPALKTV (SEQ ID NO: 16), and wherein the peptide is linked to a polycationic nucleic acid-binding component.
3. The peptide according to claim 2 , wherein the peptide is linked to the polycationic nucleic acid binding component via a spacer element.
4. A non-viral transfection mixture comprising:
(i) a lipid component,
(ii) a polycationic nucleic acid-binding component, and
(iii) the peptide PALKT (SEQ ID NO: 6) or a peptide with a length up to 30 amino acids comprising an amino acid sequence selected from the group consisting of PSNST (SEQ ID NO: 8), PPNTT (SEQ ID NO: 9), STPPNTT (SEQ ID NO: 17), APSNSTA (SEQ ID NO: 15), and SPALKTV (SEQ ID NO: 16).
5. The mixture according to claim 4 , wherein the lipid component comprises one or more lipids selected from the group consisting of cationic lipids, lipids having membrane destabilising properties, and lipids having fusogenic properties.
6. A non-viral transfection complex comprising:
(i) a nucleic acid,
(ii) a lipid component,
(iii) a polycationic nucleic acid-binding component, and
(iv) the peptide PALKT (SEQ ID NO: 6) or a peptide with a length up to 30 amino acids comprising an amino acid sequence selected from the group consisting of PSNST (SEQ ID NO: 8), PPNTT (SEQ ID NO: 9), STPPNTT (SEQ ID NO: 17), APSNSTA (SEQ ID NO: 15), and SPALKTV (SEQ ID NO: 16).
7. A process for the production of a complex according to claim 6 , which comprises admixing components (i), (ii), (iii) and (iv) in the following order: lipid component, peptide, polycationic nucleic acid binding component, and nucleic acid.
8. A non-viral transfection complex comprising:
(i) a nucleic acid,
(ii) a polycationic nucleic acid-binding component, and
(iii) the peptide PALKT (SEQ ID NO: 6) or a peptide with a length up to 30 amino acids comprising an amino acid sequence selected from the group consisting of PSNST (SEQ ID NO: 8), PPNTT (SEQ ID NO: 9), STPPNTT (SEQ ID NO: 17), APSNSTA (SEQ ID NO: 15), and SPALKTV (SEQ ID NO: 16).
9. A method of transfecting a cell with a nucleic acid, which method comprises contacting the cell in vitro or in vivo with the transfection complex according to claim 6 or claim 8 .
10. A composition comprising the transfection complex according to claim 6 or claim 8 , said composition being in admixture or conjunction with a pharmaceutically suitable carrier.
11. A method for expressing a gene in a human or in a non-human animal with a defect and/or a deficiency in a gene, which method comprises administering the transfection complex according to claim 6 or claim 8 to the human or to the non-human animal.
12. A method for inducing an immune response in a human or a non-human animal, which method comprises administering the transfection complex according to claim 6 or claim 8 to the human or to the non-human animal.
13. A method of inhibiting the expression of a gene, which comprises administering the transfection complex according to claim 6 or claim 8 to a human or to a non-human animal.
14. A kit comprising:
(i) a nucleic acid,
(ii) a polycationic nucleic acid-binding component, and
(iii) the peptide PALKT (SEQ ID NO: 6) or a peptide with a length up to 30 amino acids comprising an amino acid sequence selected from the group consisting of PSNST (SEQ ID NO: 8), PPNTT (SEQ ID NO: 9), STPPNTT (SEQ ID NO: 17), APSNSTA (SEQ ID NO: 15), and SPALKTV (SEQ ID NO: 16), and, optionally,
(iv) a lipid component.
15. The peptide according to claim 1 , wherein the peptide consists of the amino acid sequence APSNSTA [SEQ ID NO: 15].