Delivery methods and compositions for nuclease-mediated genome engineering

Abstract

The present disclosure is in the field of genome engineering, particularly targeted modification of the genome of a cell.

1 .- 11 . (canceled) 
     
     
         12 . A method of introducing a nucleic acid into a cell of a subject, the method comprising:
 administering to the subject at least one adeno-associated vector (AAV) comprising a donor molecule and at least one steroid and/or at least one B-cell inhibitor.   
     
     
         13 . The method of  claim 12 , wherein the donor molecule comprising a sequence encoding a transgene. 
     
     
         14 . The method of  claim 12 , wherein the subject is a mammal and the transgene encodes a therapeutic protein, and further wherein the mammal becomes tolerized to the therapeutic protein. 
     
     
         15 . The method of  claim 12 , wherein the subject has a hemophilia and the donor molecule encodes a clotting factor. 
     
     
         16 . The method of  claim 15 , wherein the clotting factor is Factor VIII or Factor IX. 
     
     
         17 .- 18 . (canceled) 
     
     
         19 . The method of  claim 12 , wherein the administering comprises administering at least one steroid. 
     
     
         20 . The method of  claim 19 , wherein the steroid is methylprednisolone or prednisolone. 
     
     
         21 . The method of  claim 12 , wherein the administering comprises administering at least one B-cell inhibitor. 
     
     
         22 . The method of  claim 21 , wherein the B-cell inhibitor is rituximab. 
     
     
         23 . The method of  claim 12 , wherein the at least one steroid and/or at least one B-cell inhibitor is administered after the donor molecule. 
     
     
         24 . The method of  claim 12 , wherein the at least one steroid and/or at least one B-cell inhibitor is administered simultaneously with the donor molecule. 
     
     
         25 . The method of  claim 12 , wherein the at least one steroid and/or at least one B-cell inhibitor is administered before the donor molecule. 
     
     
         26 . The method of  claim 12 , wherein the at least one steroid and the at least one B-cell inhibitor is administered.