Delivery methods and compositions for nuclease-mediated genome engineering

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.

The method of introducing a nucleic acid into a cell, the method comprising:

• administering a donor molecule comprising the nucleic acid into the cell;
• administering a nuclease to the cell, wherein the nuclease is administered 1 to 48 hours after or within 4 hours before the donor molecule and further wherein the donor molecule is integrated into the genome of the cell following cleavage by the nuclease.

A method of introducing one or more transgenes into a genome of a cell, the method comprising:

• introducing at least one nuclease into the cell, wherein the at least one nuclease cleaves the genome of the cell such that the one or more transgenes are integrated into the genome of the cell, and further wherein (i) if the donor vector is introduced into the cell before the at least one nuclease, the at least one nuclease is introduced into the cell within 48 hours after donor vector is introduced and;
• (ii) if the at least one nuclease is introduced before the donor vector, the donor vector is introduced into the cell within 4 hours after the at least one nuclease is introduced.