# Cell specific delivery of novel therapies to enhance glomerular regeneration and repair > **NIH NIH UC2** · UNIVERSITY OF WASHINGTON · 2021 · $816,153 ## Abstract PROJECT SUMMARY/ABSTRACT The goal of this project is to change the treatment paradigm for proteinuric glomerular diseases by combining therapeutics development with cell-specific delivery to enhance podocyte repair and regeneration in vivo. Podocytes, highly specialized terminally differentiated epithelial cells, are injured in the majority of glomerular diseases. As podocytes cannot self-renew, podocyte loss leads to glomerular scarring. A subpopulation of parietal epithelial cells (PECs) can serve as podocyte stem cells (`PEC progenitors'), but their regenerative potential is insufficient to overcome disease-associated glomerular damage. Enhancing productive repair of podocytes thus requires a dual synchronized approach: (i) replacing lost podocytes to increase their number, and (ii) limiting/reversing damage to the remaining podocytes. However, major knowledge gaps prevent us from achieving these goals; these include our limited knowledge on the molecular factors stimulating PEC self-renewal and podocyte regeneration/repair, as well as options methods for delivering these factors to specific kidney cell types in vivo. Our team of four expert investigators will wield complementary tools to close these knowledge gaps and produce innovative therapies. Dr. Wessely will apply Design of Experiment (DoE) approaches to identify novel combinations of molecules that increase PEC progenitors and reduce podocyte loss; Dr. Roberts will conjugate these therapeutics to VHHs (nanobodies) for delivery to PEC progenitors and podocytes; Dr. Freedman will generate gene-edited human kidney organoids to validate effects of VHHs compared to clinical data from patients; Dr. Shankland will use lineage tracing animal models of podocyte depletion and human organoids transplanted into mouse kidneys for in vivo safety and efficacy analysis. This pipeline will ultimately test the hypothesis that targeted delivery of PEC- and podocyte-specific therapeutic cargos can enhance podocyte repair and regeneration in vivo, and restore glomerular function to below the clinical disease threshold. The work will be accomplished through two Specific Aims, each with unique Milestones. The first Aim is to increase glomerular regeneration in vivo by cell targeted delivery of novel combinations of peptides and small molecules to augment podocyte progenitors of parietal epithelial cell origin. The second Aim is to increase productive repair of damaged podocytes by cell-type specific delivery of newly identified therapies. For both aims, we will employ the above pipeline to discover candidate therapeutics by DoE and cross-referenced with glomerular disease signatures from human patients. These will be combined with cell type-specific VHHs from high diversity recombinant VHH libraries to selectively deliver them to human PECs (Aim 1), or podocytes (Aim 2). Enhanced regeneration in vivo will be demonstrated in animal models of FSGS and transplanted human organoids. This process will establis... ## Key facts - **NIH application ID:** 10247521 - **Project number:** 5UC2DK126006-02 - **Recipient organization:** UNIVERSITY OF WASHINGTON - **Principal Investigator:** Stuart James Shankland - **Activity code:** UC2 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2021 - **Award amount:** $816,153 - **Award type:** 5 - **Project period:** 2020-09-01 → 2025-05-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10247521 ## Citation > US National Institutes of Health, RePORTER application 10247521, Cell specific delivery of novel therapies to enhance glomerular regeneration and repair (5UC2DK126006-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10247521. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*