Engineered clostridium botulinum toxin adapted to deliver molecules into selected cells
An engineered payload-delivery system includes a target cell binding unit, covalently bound to a pore forming unit, and a payload portion adapted with a region capable of non-covalently binding to the pore forming unit. The pore forming unit is derived from a particular sub-serotype of Clostridium toxin, while the payload region is derived from a different sub-serotype of Clostridium toxin. The disclosed chimeric protein-based composition is capable of specifically delivering payload to neural cells.
1. A polynucleotide encoding a polypeptide having a sequence at least 90% identical to SEQ ID NO 4.
2. The polynucleotide of claim 1 , wherein the encoded polypeptide has a sequence at least 95% identical to SEQ ID NO 4.
3. The polynucleotide of claim 1 , wherein the encoded polypeptide has a sequence at least 99% identical to SEQ ID NO 4.
4. The polynucleotide of claim 1 , wherein the encoded polypeptide has a sequence identical to SEQ ID NO 4.
5. A host cell comprising the polynucleotide of claim 1 .
6. The host cell of claim 5 , wherein the encoded polypeptide has a sequence at least 95% identical to SEQ ID NO 4.
7. The host cell of claim 5 , wherein the encoded polypeptide has a sequence identical to the sequence of SEQ ID NO 4.
8. The host cell of claim 5 , wherein the host cell is a bacterium or a virus.
9. The host cell of claim 5 , wherein the host cell is used to produce the polypeptide encoded by said polynucleotide in vitro.
10. The host cell of claim 7 , wherein the host cell is introduced into a subject for delivery of an agent to a target cell.
11. The host cell of claim 10 , wherein the agent comprises at least one member selected from the group consisting of a therapeutic agent, a diagnostic agent, and combinations thereof.
12. The host cell of claim 7 , wherein the polypeptide produced by the host cell is introduced into a subject for delivery of an agent to a target cell.
13. The host cell of claim 12 , wherein the agent comprises at least one member selected from the group consisting of a therapeutic agent, a diagnostic agent, and combinations thereof.
14. The host cell of claim 12 , wherein the target cell is a neuronal cell.
15. The host cell of claim 14 , wherein the target cell is a member selected from the group consisting of a cell of a brain tumor, a cell of a neuroblastoma, and a cell of a retinoblastoma, peripheral neuron; motor neuron, sensory neuron, and combination thereof.
16. A method of delivering an agent to a target cell, comprising administering a composition comprising the polynucleotide of claim 1 to a subject, wherein the subject comprises the target cell.
17. The method of claim 16 , wherein the target cell is a member selected from the group consisting of a cell of a brain tumor, a cell of a neuroblastoma, and a cell of a retinoblastoma, peripheral neuron; motor neuron, sensory neuron, and combination thereof.
18. A method of delivering an agent to a target cell, comprising administering the host cell of claim 5 to a subject, wherein the subject comprises the target cell.
19. The method of claim 18 , wherein the target cell is a member selected from the group consisting of a cell of a brain tumor, a cell of a neuroblastoma, and a cell of a retinoblastoma, peripheral neuron; motor neuron, sensory neuron, and combination thereof.