Therapeutic compositions including frataxin, lactoferrin, and mitochondrial energy generating enzymes, and uses thereof
Disclosed herein are methods and compositions for the treatment and/or prevention of diseases or conditions comprising administration of a therapeutic biological molecule, and/or naturally or artificially occurring derivatives, analogues, or pharmaceutically acceptable salts thereof, alone or in combination with one or more active agents (e.g., an aromatic-cationic peptide). The present technology provides compositions related to aromatic-cationic peptides linked to a therapeutic biological molecule and uses of the same. In some embodiments, the aromatic-cationic peptide comprises 2′,6′-dimethyl-Tyr-D-Arg-Phe-Lys-NH 2 , Phe-D-Arg-Phe-Lys-NH 2 , or D-Arg-2′,6′-Dmt-Lys-Phe-NH 2 .
1. A method for delivering an aromatic-cationic peptide and/or a therapeutic biological molecule to a cell, the method comprising contacting the cell with a peptide conjugate, wherein the peptide conjugate comprises the therapeutic biological molecule conjugated to an aromatic-cationic peptide, wherein the aromatic-cationic peptide is selected from the group consisting of: 2′,6′-dimethyl-Tyr-D-Arg-Phe-Lys-NH 2 , Phe-D-Arg-Phe-Lys-NH 2 , and D-Arg-2′,6′-Dmt-Lys-Phe-NH 2 , and wherein the therapeutic biological molecule is frataxin.
2. A method according claim 1 , wherein the therapeutic biological molecule is conjugated to the aromatic-cationic peptide by a linker.
3. A method according claim 1 , wherein the therapeutic biological molecule and aromatic-cationic peptide are chemically bonded.
4. A method according claim 1 , wherein the therapeutic biological molecule and aromatic-cationic peptide are physically bonded.
5. A method according claim 2 , wherein the aromatic-cationic peptide and the therapeutic biological molecule are linked using a labile linkage that is hydrolyzed in vivo to uncouple the aromatic-cationic peptide and the therapeutic biological molecule.
6. A method according claim 5 , wherein the labile linkage comprises an ester linkage.
7. A peptide conjugate comprising a therapeutic biological molecule conjugated to an aromatic-cationic peptide, wherein the aromatic-cationic peptide is Phe-D-Arg-Phe-Lys-NH 2 or D-Arg-2′,6′-Dmt-Lys-Phe-NH 2 , and wherein the therapeutic biological molecule is frataxin.
8. A peptide conjugate according to claim 7 , wherein the therapeutic biological molecule is conjugated to the aromatic-cationic peptide by a linker.
9. A peptide conjugate according to claim 7 , wherein the therapeutic biological molecule and aromatic-cationic peptide are chemically bonded.
10. A peptide conjugate according to claim 7 , wherein the therapeutic biological molecule and aromatic-cationic peptide are physically bonded.
11. A peptide conjugate according to claim 7 , wherein the aromatic-cationic peptide and the therapeutic biological molecule are linked using a labile linkage that is hydrolyzed in vivo to uncouple the aromatic-cationic peptide and the therapeutic biological molecule.
12. A peptide conjugate according to claim 11 , wherein the labile linkage comprises an ester linkage.