Abstract: TH-PO0142
Human Kidney Organoid Platform to Systematically Evaluate Adeno-Associated Virus Serotype Tropism and Podocyte Gene Delivery Efficiency
Session Information
- Integrative Genomics and Multi-Omics in Noncystic Genetic Kidney Disease
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic (Complex and Non-Cystic Monogenic)
Authors
- Prakash, Chiranth M., Boston Children's Hospital, Boston, Massachusetts, United States
- Schneider, Ronen, Boston Children's Hospital, Boston, Massachusetts, United States
- Nelson, Becca, Stanford Medicine, Stanford, California, United States
- Saida, Ken, Boston Children's Hospital, Boston, Massachusetts, United States
- Lomjansook, Kraisoon, Boston Children's Hospital, Boston, Massachusetts, United States
- Franken, Gijs AC, Boston Children's Hospital, Boston, Massachusetts, United States
- Riedhammer, Korbinian M., Boston Children's Hospital, Boston, Massachusetts, United States
- Marchuk, Daniel, Boston Children's Hospital, Boston, Massachusetts, United States
- Balbach, Maximilian, Boston Children's Hospital, Boston, Massachusetts, United States
- Madariaga, Leire, Boston Children's Hospital, Boston, Massachusetts, United States
- Zion, Elena, Boston Children's Hospital, Boston, Massachusetts, United States
- Hildebrandt, Friedhelm, Boston Children's Hospital, Boston, Massachusetts, United States
Background
Efficient, cell-type specific gene delivery to distinct nephron compartments remains a major barrier to developing gene therapies for nephrotic diseases. Selective targeting of podocytes and proximal tubule cells in human derived systems remains a challenge. Here, we utilized human iPSC derived kidney organoids to systematically evaluate adeno-associated virus (AAV) serotype tropism across nephron-like structures.
Methods
Human iPSC-derived kidney organoids and cultured podocyte cell lines were used to evaluate AAV tropism across complementary 2D and 3D systems. Kidney organoids containing podocyte-like and tubular epithelial compartments were employed as a physiologically relevant model of human nephrogenesis. In parallel, differentiated podocyte cell lines were used for controlled AAV screening. A panel of AAV serotypes/engineered capsids (AAV2, AAV6, AAV8, KP1, and additional serotypes) expressing fluorescent reporter constructs was applied. Transduction efficiency and cell type specificity were assessed by immunofluorescence co-localization with nephron segment markers.
Results
In podocyte cell lines, AAV2 demonstrated efficient baseline transduction. Engineered capsids AAV2-7m8 and AAV-DJ increased transduction efficiency by ~1.5-fold relative to AAV2, with AAV2-7m8 achieving the highest enhancement, approaching a 2-fold increase. In kidney organoids, AAV-KP1 demonstrated preferential transduction of proximal tubule cells, as evidenced by co-localization with proximal tubule markers within organoid structures. Other AAV serotypes/capsids showed low and heterogeneous distribution across glomerular and tubular compartments, indicating differential nephron segment tropism within the organoid system.
Conclusion
Human kidney organoids enable scalable mapping of AAV tropism at nephron resolution. AAV-KP1 preferentially targets proximal tubules, supporting organoids as an useful platform for optimizing kidney-directed gene delivery. Future work will optimize capsid selection to improve transduction in mice and human kidney organoids.
Funding
- Private Foundation Support