Transport Molecules Using Reverse Sequence HIV-TAT Polypeptides
This invention relates to novel transport molecules that comprise a polypeptide comprising amino acid residues arranged in a sequence that is the reverse-sequence of basic portion of the HIV-TAT protein. The novel transport polypeptides are useful for transmembrane or intracellular delivery of cargo molecules, non-limiting examples of which include polypeptides and nucleic acids. The novel transport polypeptides may be covalently or non-covalently bound to the cargo modules.
1 . A transport molecule for the delivery of a cargo molecule, wherein said transport molecule comprises a reverse-sequence polypeptide having an amino acid sequence according to SEQ ID NO 1.
2 . The transport molecule according to claim 1 , wherein the reverse-sequence polypeptide is covalently attached to the cargo molecule.
3 . The transport molecule according to claim 1 , wherein the reverse-sequence polypeptide is covalently bound to a positively-charged backbone that is non-covalently attached to the cargo molecule.
4 . The transport molecule according to claim 3 , wherein the reverse-sequence polypeptide is covalently bound to a positively charged backbone that is non-covalently bound to the cargo molecule.
5 . The transport molecule according to claim 1 , wherein said transport molecule increases the penetration of the cargo molecule through a biological membrane.
6 . The transport molecule according to claim 5 , wherein the biological membrane is found in the skin.
7 . The transport molecule of claim 1 , wherein said transport molecule increases the intracellular penetration of the cargo molecule.
8 . A conjugate for the delivery of a cargo molecule, said conjugate comprising
a transport molecule comprising a reverse-sequence polypeptide having an amino acid sequence as set forth in SEQ ID NO. 1;
and a cargo molecule.
9 . The conjugate according to claim 8 , wherein said transport molecule is covalently attached to said cargo molecule.
10 . The conjugate according to claim 8 , wherein said transport molecule is non-covalently attached to said cargo molecule.
11 . The conjugate according to claim 8 , wherein said cargo molecule is a therapeutic agent.
12 . The conjugate according to claim 11 , wherein said therapeutic agent is selected from the group consisting of peptides, proteins, oligonucleotides, enzymes, and antigens.
13 . The conjugate according to claim 11 , wherein said therapeutic agent derived from a serotype of botulinum toxin or a fragment thereof.
14 . The conjugate according to claim 13 , wherein said diagnostic agent is selected from the group consisting of radiopaque contrast agents, paramagnetic contrast agents, superparamagnetic contrast agents, and CT contrast agents.
15 . A method for the treatment of a disease, wherein said method comprises
selecting a cargo molecule;
selecting a transport molecule;
binding said cargo molecule to said transport molecule either covalently or non-covalently to form a cargo molecule/transport molecule conjugate; and
administering said conjugate to target cells or to a membrane in order to cause intracellular or transmembrane delivery of the cargo molecule.