Original Article

Gene Therapy (2017) 24, 308–313; doi:10.1038/gt.2017.21; published online 13 April 2017

AAV9-mediated engineering of autotransplanted kidney of non-human primates

S Tomasoni1, P Trionfini1, N Azzollini1, L Zentilin2, M Giacca2,3, S Aiello1, L Longaretti1, E Cozzi4,5, N Baldan6, G Remuzzi1,7,8 and A Benigni1

  1. 1IRCCS – Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy
  2. 2Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy
  3. 3Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy
  4. 4Department of Cardiac, Thoracic and Vascular Sciences, Transplant Immunology Unit, Padua University Hospital, Padova, Italy
  5. 5Consortium for Research in Organ Transplantation (CORIT), Padua, Italy
  6. 6Department of Surgical, Oncological and Gastroenterological Sciences, Padua University Hospital, Padova, Italy
  7. 7Unit of Nephrology and Dialysis, Azienda Socio-Sanitaria Territoriale (ASST) Papa Giovanni XXIII, Bergamo, Italy
  8. 8Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy

Correspondence: Professor G Remuzzi, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Via Stezzano, 87, Bergamo 24126, Italy. E-mail: giuseppe.remuzzi@marionegri.it

Received 6 December 2016; Revised 21 February 2017; Accepted 16 March 2017
Accepted article preview online 27 March 2017; Advance online publication 13 April 2017



Ex vivo gene transfer to the graft before transplantation is an attractive option for circumventing systemic side effects of chronic antirejection therapy. Gene delivery of the immunomodulatory protein cytotoxic T-lymphocyte-associated protein 4–immunoglobulin (CTLA4-Ig) prevented chronic kidney rejection in a rat model of allotransplantation without the need for systemic immunosuppression. Here we generated adeno-associated virus type 2 (AAV2) and AAV9 vectors encoding for LEA29Y, an optimized version of CTLA4-Ig. Both LEA29Y vectors were equally efficient for reducing T-cell proliferation in vitro. Serotype 9 was chosen for in vivo experiments owing to a lower frequency of preformed antibodies against the AAV9 capsid in 16 non-human primate tested sera. AAV9-LEA29Y was able to transduce the kidney of non-human primates in an autotransplantation model. Expression of LEA29Y mRNA by renal cells translated into the production of the corresponding protein, which was confined to the graft but not detected in serum. Results in non-human primates represent a step forward in maintaining the portability of this strategy into clinics.