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Cell specific delivery of novel therapies to enhance glomerular regeneration and repair

Key Personnel

Stuart Shankland (Contact PI)
University of Washington

  • Jeffrey W. Pippin
    University of Washington

Benjamin S. Freedman (PI)
University of Washington

  • Laura Mariani
    University of Washington

James M. Roberts (PI)
Lumen Bioscience

  • Kristie Keeney
    Lumen Bioscience

Oliver Wessely (PI)
Cleveland Clinic

  • Lauren Haines
    Cleveland Clinic
  • Uyen Tran
    Cleveland Clinic

Project Description

The overall goal of this project is to change the treatment paradigm for proteinuric glomerular diseases by combining therapeutics development with cell-specific delivery to enhance endogenous podocyte regeneration and repair.

We will 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. Studies will also increase productive repair of damaged podocytes by cell-type specific delivery of newly identified therapies. We will discover candidate therapeutics by a Design of Experiment approach DoE that are then cross-referenced with glomerular disease signatures from human patients. These will be combined with cell type-specific VHHs (nanobodies) from high diversity recombinant VHH libraries to selectively deliver them to human PECs or podocytes. Enhanced regeneration in vivo will be demonstrated in animal models of FSGS and transplanted human organoids. This process will establish a new paradigm for the treatment of kidney disease, and produce lead therapeutic candidates for further pre-clinical development and ultimately human clinical trials.