title: AAV9-mediated engineering of autotransplanted kidney of non-human primates.
abstract: 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.
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Tomasoni
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Trionfini
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Azzollini
authors.affiliation: Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Zentilin
authors.affiliation: Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy.|Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Giacca
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Aiello
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Longaretti
authors.affiliation: Department of Cardiac, Thoracic and Vascular Sciences, Transplant Immunology Unit, Padua University Hospital, Padova, Italy.|Consortium for Research in Organ Transplantation (CORIT), Padua, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Cozzi
authors.affiliation: Department of Surgical, Oncological and Gastroenterological Sciences, Padua University Hospital, Padova, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Baldan
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy.|Unit of Nephrology and Dialysis, Azienda Socio-Sanitaria Territoriale (ASST) Papa Giovanni XXIII, Bergamo, Italy.|Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Remuzzi
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Benigni
mesh_terms: D000069594:Abatacept / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D000229:Dependovirus / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006084:Graft Rejection / Q000209:etiology / Q000628:therapy*; D057809:HEK293 Cells; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D008252:Macaca fascicularis; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology; D014182:Transplantation, Autologous / Q000009:adverse effects
chemical_list: D000069594:Abatacept