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

Gene Therapy volume 24, pages 308–313 (2017)Cite this article

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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.

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Acknowledgements

We thank Kerstin Mierke for editing the manuscript. We are also grateful to the staff of CORIT and of the University of Padua for the assistance provided during the in vivo studies. This work was supported by Fondazione CARIPLO and Fondazione Cassa di Risparmio di Padova e Rovigo (CARIPARO).

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Authors and Affiliations

  1. IRCCS – Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy

    S Tomasoni, P Trionfini, N Azzollini, S Aiello, L Longaretti, G Remuzzi & A Benigni

  2. Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy

    L Zentilin & M Giacca

  3. Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy

    M Giacca

  4. Department of Cardiac, Thoracic and Vascular Sciences, Transplant Immunology Unit, Padua University Hospital, Padova, Italy

    E Cozzi

  5. Consortium for Research in Organ Transplantation (CORIT), Padua, Italy

    E Cozzi

  6. Department of Surgical, Oncological and Gastroenterological Sciences, Padua University Hospital, Padova, Italy

    N Baldan

  7. Unit of Nephrology and Dialysis, Azienda Socio-Sanitaria Territoriale (ASST) Papa Giovanni XXIII, Bergamo, Italy

    G Remuzzi

  8. Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy

    G Remuzzi

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  1. S Tomasoni
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  2. P Trionfini
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  3. N Azzollini
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  4. L Zentilin
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  6. S Aiello
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  7. L Longaretti
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  8. E Cozzi
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  9. N Baldan
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  10. G Remuzzi
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  11. A Benigni
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Corresponding author

Correspondence to G Remuzzi.

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The authors declare no conflict of interest.

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Tomasoni, S., Trionfini, P., Azzollini, N. et al. AAV9-mediated engineering of autotransplanted kidney of non-human primates. Gene Ther 24, 308–313 (2017). https://doi.org/10.1038/gt.2017.21

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  • DOI: https://doi.org/10.1038/gt.2017.21

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