Production of a biological factor and creation of an immunologically privileged environment using genetically altered sertoli cells

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.

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. 
     
     
         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. 
     
     
         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. 
     
     
         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. 
     
     
         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 10 5  to 10 10  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. 
     
     
         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. 
     
     
         19 . The vector of  claim 8  further comprising a 3′ termination sequence which functions in Sertoli cells. 
     
     
         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 .