| Autor: |
Wu G; III. Department of Medicine.; Hamburg Center for Kidney Health (HCKH)., Liu S; III. Department of Medicine.; Hamburg Center for Kidney Health (HCKH)., Hagenstein J; III. Department of Medicine.; Hamburg Center for Kidney Health (HCKH)., Alawi M; Bioinformatics Core., Hengel FE; III. Department of Medicine.; Hamburg Center for Kidney Health (HCKH)., Schaper M; III. Department of Medicine.; Hamburg Center for Kidney Health (HCKH)., Akyüz N; Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, and., Liao Z; III. Department of Medicine.; Hamburg Center for Kidney Health (HCKH)., Wanner N; III. Department of Medicine.; Hamburg Center for Kidney Health (HCKH)., Tomas NM; III. Department of Medicine.; Hamburg Center for Kidney Health (HCKH)., Failla AV; Microscopy Imaging Facility, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Dierlamm J; Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, and., Körbelin J; Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, and., Lu S; III. Department of Medicine.; Hamburg Center for Kidney Health (HCKH)., Huber TB; III. Department of Medicine.; Hamburg Center for Kidney Health (HCKH). |
| Abstrakt: |
Adeno-associated virus (AAV) is a promising in vivo gene delivery platform showing advantages in delivering therapeutic molecules to difficult or undruggable cells. However, natural AAV serotypes have insufficient transduction specificity and efficiency in kidney cells. Here, we developed an evolution-directed selection protocol for renal glomeruli and identified what we believe to be a new vector termed AAV2-GEC that specifically and efficiently targets the glomerular endothelial cells (GEC) after systemic administration and maintains robust GEC tropism in healthy and diseased rodents. AAV2-GEC-mediated delivery of IdeS, a bacterial antibody-cleaving proteinase, provided sustained clearance of kidney-bound antibodies and successfully treated antiglomerular basement membrane glomerulonephritis in mice. Taken together, this study showcases the potential of AAV as a gene delivery platform for challenging cell types. The development of AAV2-GEC and its successful application in the treatment of antibody-mediated kidney disease represents a significant step forward and opens up promising avenues for kidney medicine. |
