Method and carrier complexes for delivering molecules to cells

• US 9,315,586 B2
• Filed: 03/16/2012
• Issued: 04/19/2016
• Est. Priority Date: 05/01/2003
• Status: Active Grant

• Current Assignee: Cornell Research Foundation Incorporated (Cornell University)
• Original Assignee: Cornell Research Foundation Incorporated (Cornell University)
• Inventors: Szeto, Hazel, Zhao, Kesheng, Robertson, Hugh, Birk, Alex V.
• Primary Examiner(s): Alstrum Acevedo, James H
• Assistant Examiner(s): Martinez, Tara
• Application Number:
  US13/422,722
• Publication Number:
  US 20130085259A1
• Time in Patent Office: 1,495 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 31/713 Double-stranded nucleic acids or oligonucleotides
• CPC Class Codes: A61K 38/47 acting on glycosyl compounds (3.2), e.g. cellulases, lactases
• CPC Class Codes: A61K 47/64 Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent peptidic linkers A61K47/65
• CPC Class Codes: A61K 47/645 Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 39/00 General protective or antinoxious agents
• CPC Class Codes: A61P 39/06 Free radical scavengers or antioxidants
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 17/00 Carrier-bound or immobilised peptides carrier-bound or immobilised enzymes C12N11/00; Preparation thereof
• CPC Class Codes: C07K 5/08 Tripeptides
• CPC Class Codes: C07K 5/1016 and aromatic or cycloaliphatic
• CPC Class Codes: C07K 5/1019 with the first amino acid being basic
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 15/87 : Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
• CPC Class Codes: C12N 2310/3513 : Protein; Peptide
• CPC Class Codes: C12N 2320/32 : Special delivery means, e.g. tissue-specific
• CPC Class Codes: C12N 9/2471 : Beta-galactosidase (3.2.1.23), i.e. exo-(1-->4)-beta-D-galactanase
• CPC Class Codes: C12N 9/96 : Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates
• CPC Class Codes: C12Y 302/01023 : Beta-galactosidase (3.2.1.23), i.e. exo-(1-->4)-beta-D-galactanase

Abstract

The invention relates to carrier complexes and methods for delivering molecules to cells. The carrier complexes comprises a molecule and an aromatic cationic peptide in accordance with the invention. In one embodiment, the method for delivering a molecule to a cell comprises contacting the cell with a carrier complex. In another embodiment, the method for delivering a molecule to a cell comprises contacting the cell with a molecule and an aromatic cationic peptide.

Claims

1. A method for delivering a molecule to a cell, the method comprising contacting the cell with a carrier complex, wherein the carrier complex comprises the molecule conjugated to an aromatic cationic peptide, wherein the aromatic cationic peptide is selected from the group consisting of:

Tyr-D-Arg-Phe-Lys-NH₂ (DALDA), 2′

,6′

-Dmt-D-Arg-Phe-Lys-NH₂ (Dmt¹-DALDA), Phe-D-Arg-Phe-Lys-NH₂ (Phe¹-DALDA), D-Arg-2′

,6′

-Dmt-Lys-Phe-NH₂, and 2′

,6′

-Dmp-D-Arg-Phe-Lys-NH₂ (Dmp¹-DALDA); and

wherein the molecule is a lipid.

2. A method according to claim 1, wherein the peptide has the formula Tyr-D-Arg-Phe-Lys-NH₂ (DALDA).

3. A method according to claim 1, wherein the peptide has the formula 2′

,6′

-Dmt-D-Arg-Phe-Lys-NH₂ (Dmt¹-DALDA).

4. A method according to claim 1, wherein the peptide has the formula Phe-D-Arg-Phe-Lys-NH₂ (Phe¹-DALDA).

5. A method according to claim 1, wherein the peptide has the formula D-Arg-2′

,6′

-Dmt-Lys-Phe-NH₂.

6. A method according to claim 1, wherein the peptide has the formula 2′

,6′

-Dmp-D-Arg-Phe-Lys-NH₂ (Dmp¹-DALDA).

7. A method according to claim 1, wherein the cell is a bacterial cell.

8. A method according to claim 1, wherein the cell is a plant cell.

9. A method according to claim 1, wherein the cell is an animal cell.

10. A method according to claim 9, wherein the animal cell is a mammalian cell.

11. A method according to claim 9, wherein the cell is a neuronal cell.

12. A method according to claim 9, wherein the cell is a renal epithelial cell.

13. A method according to claim 9, wherein the cell is an intestinal epithelial cell.

14. A method according to claim 9, wherein the cell is a vascular endothelial cell.

15. A method according to claim 14, wherein the endothelial cell is a blood-brain barrier endothelial cell.

16. A method according to claim 9, wherein the cell is a glial cell.

17. A method according to claim 9, wherein the cell is a hepatocyte.

18. A method according to claim 1, wherein the aromatic-cationic peptide comprises a linker.

19. A method according to claim 1, wherein the molecule comprises a linker.

20. A method according to claim 1, wherein the molecule and aromatic cationic peptide are chemically bonded.