Methods for the delivery of therapeutic agents to donor organs

1 . A method of administering a therapeutic agent to a human donor organ, the method comprising:

maintaining the human donor organ under normothermic ex vivo perfusion conditions prior to transplant into a human subject in need of an organ transplant, wherein the therapeutic agent comprises a viral vector comprising a transgene, wherein the transgene is under control of a promoter and encodes a protein that mitigates graft dysfunction or allograft vasculopathy;

wherein the human donor organ is allogeneic or autologous to the human subject;

wherein the therapeutic agent is circulated in the perfusion conditions comprising a perfusion solution mixture comprising washed red blood cells substantially free of plasma and serum reconstituted with isotonic non-pyrogenic intravenous (IV) crystalloid solution, albumin, and heparin, and a priming solution comprising albumin, ciprofloxacin, cefazolin, adult multivitamins, sodium bicarbonate, methylprednisolone, calcium gluconate, and dextrose; and

wherein the viral vector is an adeno-associated viral vector.

2 . The method of claim 1 wherein the human donor organ is a heart and the subject needs a donor heart.

3 . The method of claim 1 wherein the human donor organ is a kidney and the subject needs a donor kidney, wherein the donor organ is a liver and the subject needs a donor liver, or wherein the human donor organ is a lung and the subject needs a donor lung.

4 . The method of claim 1 wherein the ex vivo perfusion conditions are maintained using a Langendorff perfusion system or a warm blood perfusion system.

5 . The method of claim 1 wherein circulating the therapeutic agent through the human donor organ while maintaining the perfusion conditions comprises:

a. harvesting the human donor organ and blood from the human donor;

b. priming the ex vivo perfusion circuit with the perfusion solution mixture;

c. adding the therapeutic agent to the ex vivo perfusion circuit and placing the human donor organ on the ex vivo perfusion device; and

d. perfusing the human donor organ.

6 . The method of claim 5 wherein perfusing the human donor organ comprises perfusion for 2 or more hours.

7 . The method of claim 1 further comprising subsequently transplanting the human donor organ into the human subject in need thereof.

8 . A method of modifying a human donor organ prior to transplantation, the method comprising:

maintaining the human donor organ under normothermic ex vivo perfusion conditions and administering a viral vector encoding a transgene to the human donor organ and circulating the viral vector through the human donor organ;

wherein the transgene is under control of a promoter and encodes a protein that mitigates graft dysfunction or allograft vasculopathy;

wherein the viral vector is circulated in the perfusion conditions comprising red blood cells substantially free of plasma and serum reconstituted with isotonic non-pyrogenic IV crystalloid solution, albumin, and heparin, and a priming solution comprising albumin, ciprofloxacin, cefazolin, adult multivitamins, sodium bicarbonate, methylprednisolone, calcium gluconate, and dextrose; and

wherein the viral vector is an adeno-associated viral vector.

9 . The method of claim 8 wherein circulating the viral vector through the human donor organ comprises circulation for 2 or more hours.

10 . A method of treating organ failure in a subject, the method comprising:

transplanting a human donor organ into a human subject in need thereof, wherein a viral vector encoding a transgene has been administered to a human donor organ prior to transplantation by a method comprising maintaining the human donor organ under normothermic ex vivo perfusion conditions prior to the transplantation and circulating the viral vector through the human donor organ in the perfusion conditions; wherein the transgene is under control of a promoter and expresses a protein that mitigates graft dysfunction or allograft vasculopathy; wherein the human donor organ is allogeneic or autologous to the human subject; wherein the viral vector is circulated in a perfusion solution mixture comprising washed red blood cells substantially free of plasma and serum reconstituted with isotonic non-pyrogenic IV crystalloid solution, albumin, and heparin, and a priming solution comprising albumin, ciprofloxacin, cefazolin, adult multivitamins, sodium bicarbonate, methylprednisolone, calcium gluconate, and dextrose; and wherein the viral vector is an adeno-associated viral vector.

11 . The method of claim 10 wherein the subject in need thereof has organ failure, wherein the organ failure is heart failure, and wherein the human donor organ is a donor heart.

12 . The method of claim 10 wherein circulating the viral vector through the human donor organ comprises circulation for 2 or more hours.