PRODUCTION OF A BIOLOGICAL FACTOR AND CREATION OF AN IMMUNOLOGICALLY PRIVILEGED ENVIRONMENT USING GENETICALLY ALTERED SERTOLI CELLS

• US 20080145348A1
• Filed: 02/20/2008
• Published: 06/19/2008
• Est. Priority Date: 11/06/1998
• Status: Abandoned Application

• Current Assignee: Sertoli Technologies, Inc. (Sernova Corporation)
• Original Assignee: Sertoli Technologies, Inc. (Sernova Corporation)
• Inventors: Kirkpatrick, Shaun A., Halberstadt, Craig, Gores, Paul
• Application Number:
  US12/034,305
• Publication Number:
  US 20080145348A1
• Time in Patent Office: Days
• US Class Current: 424/93.21
• CPC Class Codes: A61K 2035/122 for inducing tolerance or supression of immune responses
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 38/4846 Factor VII (3.4.21.21); Factor IX (3.4.21.22); Factor Xa (3.4.21.6); Factor XI (3.4.21.27); Factor XII (3.4.21.38)
• 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 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C12N 5/0683 Cells of the male genital tract, e.g. prostate, epididymis; Non-germinal cells from testis, e.g. Leydig cells, Sertoli cells spermatogonia C12N5/061
• CPC Class Codes: C12N 9/1051 Hexosyltransferases (2.4.1)
• CPC Class Codes: C12N 9/644 Coagulation factor IXa (3.4.21.22)
• CPC Class Codes: C12Y 304/21022 Coagulation factor IXa (3.4.21.22)

Abstract

The present invention provides a method of providing an individual with a biological factor or intermediate thereof which comprises introducing into the individual Sertoli cells genetically altered to produce the biological factor or intermediate thereof. The genetically altered Sertoli cells are administered in an amount effective to produce the desired effect. Aside from producing the biological factor or intermediate thereof, the engineered Sertoli cells also create an immunologically privileged site. Vectors comprising a promoter which functions in Sertoli cells operably linked to coding sequence for a desired biological factor are also provided as are Sertoli cells comprising such vectors. A pharmaceutical composition comprising Sertoli cells genetically altered to produce a biological factor is also provided.

Claims

1. A method for providing an individual with a biological factor or intermediate thereof which comprises introducing into said individual a therapeutically effective amount of Sertoli cells, said Sertoli cells genetically altered to produce said biological factor or intermediate thereof and wherein said Sertoli cells create an immunologically privileged site.

3. The method of claim 1 or 2 wherein said subject is a mammal.

4. The method of claim 3 wherein said mammal is human.

5. The method of claim 1 or 2 wherein said biological factor is a hormone.

6. The method of claim 3 wherein said biological factor is a hormone.

10. The method of claim 1 or 2 wherein said introduction is by transplantation.

11. The method of claim 1 or 2 wherein said Sertoli cells are introduced into said individual in a dosage ranging from 10⁵ to 10¹⁰ cells.

12. The method of claim 10 wherein said transplantation is by xenograft.

13. The method of claim 10 wherein said transplantation is by allograft.

2. A method of treating a disease that results from a deficiency of a biological factor which comprises introducing into a subject in need of such treatment, a therapeutically effective amount of Sertoli cells, said Sertoli cells genetically altered to produce said biological factor or intermediate thereof and wherein said Sertoli cells create an immunologically privileged site.

7. The method of claim 2 wherein said biological factor is insulin and said disease is diabetes mellitus.

8. The method of claim 2 wherein said biological factor is Factor IX and said disease is hemophilia B.

9. The method of claim 2 wherein said biological factor is B-UGT and said disease is Crigler-Najjar (CN) disease.

19. The vector of claim 8 further comprising a 3′

termination sequence which functions in Sertoli cells.

14. A pharmaceutical composition comprising Sertoli cells genetically altered to produce a biological factor or intermediate thereof admixed with a pharmaceutically acceptable carrier.

15. The pharmaceutical composition of claim 14 wherein said biological factor is a hormone.

16. A compartmentalized kit comprising a first container adapted to contain Sertoli cells genetically altered to produce a biological factor or intermediate thereof.

17. The compartmentalized kit of claim 16 further comprising a second container adapted to contain a pharmaceutically acceptable carrier.

18. A vector comprising in the 5′

to 3′

direction a promoter which functions in Sertoli cells operatively linked to a coding sequence for a biological factor or intermediate.

20. The vector of claim 18 or 19 further comprising a signal sequence coding for a signal peptide, said signal sequence located downstream from said promoter and upstream to said coding sequence for a biological factor or intermediate.

21. The vector of claim 18 or 19 wherein the coding sequence is the coding sequence for human factor IX.

22. The vector of claim 20 wherein the coding sequence is the coding sequence for human factor IX.

23. The vector of claim 18 or 19 wherein the coding sequence is the coding sequence for B-UGT.

24. The vector of claim 20 wherein the coding sequence is the coding sequence for B-UGT.

25. A Sertoli cell comprising the vector of claim 18 or 19.

26. A Sertoli cell comprising the vector of claim 20.