Retrograde transport peptide and use of same for delivery to central nervous system
Transport peptides, alone or attached to a cargo moiety, are capable of targeted axonal import into the spinal cord and other structures of the central nervous system. The transport peptides can be used to deliver therapeutic agents and other molecules of interest from the periphery to the central nervous system, providing a means to detect, treat or prevent neurodegenerative diseases, stroke, chronic pain and other conditions via minimally invasive techniques of administration.
1. A recombinant or synthetic transport peptide, or polynucleotide encoding same, or a derivative thereof having at least one amino acid or nucleic acid substituted with a non-natural derivative of the indicated amino acid or nucleic acid, wherein the peptide comprises the amino acid sequence QSQSQMR (SEQ ID NO: 1), or TSTAPHLRLRLTSR (SEQ ID NO: 7), and wherein the transport peptide further comprises a heterologous molecule attached thereto by chemical conjugation or expression as a fusion partner.
2. The transport peptide of claim 1 , wherein the heterologous molecule is a polypeptide, antibody, polynucleotide, vector, delivery vehicle, small molecule or drug.
3. The transport peptide of claim 1 , wherein the polypeptide is an enzyme or a growth factor.
4. The transport peptide of claim 1 , wherein the polynucleotide is a siRNA molecule.
5. The transport peptide of claim 1 , which is a fusion protein comprising the transport peptide fused with a heterologous peptide.
6. The fusion protein of claim 5 , wherein the heterologous peptide is selected from the group consisting of enzymes, growth factors, antibodies, and therapeutic peptides.
7. The transport peptide of claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO: 1.
8. The transport peptide of claim 1 , further comprising a flanking sequence that mediates incorporation into a carrier.
9. The transport peptide of claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO: 8.
10. The transport peptide of claim 1 , wherein the non-natural derivative is a D-amino acid, β-amino acid, or a chemically modified amino acid.
11. The transport peptide of claim 1 , wherein the peptide exhibits at least 90% identity with SEQ ID NO: 7 or 8.
12. The transport peptide of claim 1 , wherein the peptide is fewer than 50 amino acids in length.
13. The transport peptide of claim 1 , wherein the peptide is 10-20 amino acids in length.
14. A method of delivering a molecule to a central nervous system (CNS) site of a subject, the method comprising administering the transport peptide of claim 1 to a peripheral site of the subject.
15. The method of claim 14 , wherein the administering comprises intramuscular administration, intraperitoneal administration, intranasal administration, intravenous administration or subcutaneous administration.
16. The method of claim 14 , wherein the CNS site is the spinal cord.
17. The method of claim 14 , wherein the molecule delivered is a therapeutic agent.
18. The method of claim 17 , wherein the therapeutic agent is a small molecule, polypeptide, antibody, polynucleotide, or drug.
19. A method of treating a CNS condition in a subject, the method comprising administering to a peripheral site of the subject the transport peptide of claim 1 , wherein the heterologous molecule is a therapeutic agent.
20. The method of claim 19 , wherein the CNS condition is a neurodegenerative disease, stroke or chronic pain.