Vector system

• US 20040071675A1
• Filed: 05/05/2003
• Published: 04/15/2004
• Est. Priority Date: 11/03/2000
• Status: Abandoned Application

• Current Assignee: Oxford Biomedica (UK) Limited
• Original Assignee: Oxford Biomedica (UK) Limited
• Inventors: Azzouz, Mimoun, Mazarakis, Nicholas
• Application Number:
  US10/429,608
• Publication Number:
  US 20040071675A1
• Time in Patent Office: Days
• US Class Current: 424/93.21
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C12N 2810/6081 rhabdoviridae, e.g. VSV

Abstract

There is provided the use of a vector system comprising at least part of a rabies g protein, to transduce a TH positive neuron. There is also provided the use of a rabies G vector system to transduce a target site, in which the vector system travels to the target site by retrograde transport, which may comprise the step of administration of the vector system to an administration site which is distant from the target site.

Claims

1. A method of delivering an entity of interest (EOI) to a tyrosine hydroxylase(TH) positive neuron, said method comprising a vector system comprising at least a part of a rabies G protein or a mutant, variant, homologue or fragment thereof, wherein said vector system delivers said EOI to said TH positive neuron.

2. The method according to claim 1, wherein the vector system is pseudotyped with at least a part of a rabies G protein or a mutant, variant, homologue or fragment thereof.

3. The method according to claim 1, further comprising treating and/or preventing a disease associated with death or impaired function of TH positive neurons.

4. The method according to claim 3, wherein said disease is Parkinson'"'"'s disease.

5. A method for analysing the effect of a protein of interest (POI) in a TH positive neuron, comprising the method of claim 1.

6. A method for analysing a function of a gene, or a protein encoded by a gene, in a TH positive neuron, wherein said method comprises a step of inhibiting or blocking expression of said gene, or causing overexpression of said gene, comprising said method of claim 1.

7. A TH positive neuron transduced with a vector system comprising at least a part of a rabies G protein or a mutant, variant, homologue or fragment thereof.

8. The TH positive neuron of claim 7, wherein the vector system is pseudotyped with at least a part of a rabies G protein or a mutant, variant, homologue or fragment thereof.

9. The TH positive neuron of claim 7, wherein said neuron is immortalised.

10. A pharmaceutical composition comprising said TH positive neuron of claim 7.

11. A method for treating and/or preventing a disease in a subject in need of same, said method comprising transplanting a composition comprising a genetically manipulated TH positive neuron transduced with a vector system comprising at least a part of a rabies G protein or a mutant, variant, homologue or fragment thereof into said subject.

12. A method of delivering an EOI to a target site, said method comprising a vector system comprising at least a part of a rabies G protein or a mutant, variant, homologue or fragment thereof, wherein said vector system travels to said target site by retrograde transport.

13. The method according to claim 12, wherein said vector system is pseudotyped with at least a part of a rabies G protein or a mutant, variant, homologue or fragment thereof.

14. The method according to claim 12, further comprising a step of administrating said vector system to an administration site which is distant from the target site, wherein said vector system travels from said administration site to said target site by retrograde transport.

15. The method according to claim 14, wherein said administration site is a peripheral site.

16. The method according to claim 12, wherein said administering is intramuscular.

17. The method according to claim 12, wherein said target site is a cell in the CNS.

18. The method according to claim 12, wherein said target site is a motoneuron.

19. The method according to claim 12, wherein said target site is a sensory neuron.

20. A method of treating and/or preventing pain comprising the method of claim 19.

22. A method of treating and/or preventing a disease in a subject in need of same, said method comprising said method of claim 12.

21. A pharmaceutical composition in an effective amount for treating and/or preventing a disease in a subject in need of same, said composition comprising a vector system comprising at least a part of a rabies G protein or a mutant, variant, homologue or fragment thereof, wherein said vector system travels to a target site by retrograde transport.

23. A method for delivering an EOI to a neuron in the CNS comprising administrating a vector system to a peripheral site, wherein said vector system comprises at least a part of a rabies G protein or a mutant, variant, homologue or fragment thereof, and retrograde transport of said vector system or part thereof to the neuron.