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Published on: August 10, 2018
Combination siRNA delivery as a therapeutic strategy for ADPKD
Joshua Giblin1, Isabella Suzuki1, Yi Huang1
1Alfred E. Mann Department of Biomedical Engineering, University of Southern California, Los Angeles, California 90089, USA.
Biorxiv : the Preprint Server for Biology
|August 1, 2026
Summary
Autosomal dominant polycystic kidney disease (ADPKD) therapies improved by dual gene silencing. Peptide amphiphile micelles targeting collecting duct epithelia delivered siRNA to reduce cyst growth and inflammation in ADPKD models.
Area of Science:
- Nephrology
- Genetics
- Nanomedicine
Background:
- Autosomal dominant polycystic kidney disease (ADPKD) is a prevalent genetic kidney disorder with limited targeted treatments.
- Cyst growth and inflammation are hallmarks of ADPKD, driven by mediators like TMEM16A and MCP-1 in collecting duct epithelia.
Purpose of the Study:
- To investigate the therapeutic potential of simultaneously silencing TMEM16A and MCP-1 in ADPKD.
- To develop a targeted nanoparticle delivery system for dual gene silencing in kidney collecting duct epithelia.
Main Methods:
- Utilized peptide amphiphile micelles (PAMs) functionalized with a collecting duct-targeting peptide (CDM) for siRNA delivery.
- Co-delivered siRNA targeting Tmem16a and Mcp-1 to an inducible Pkd1-deficient mouse model of ADPKD.
- Assessed kidney pathology, cyst burden, and inflammatory cell infiltration.
Main Results:
- Dual gene silencing of Tmem16a and Mcp-1 significantly reduced kidney enlargement, cystic burden, tubular injury, and macrophage infiltration in ADPKD mice.
- CDM-mediated delivery showed superior efficacy compared to non-targeted siRNA delivery.
- Enhanced uptake and dual gene silencing were observed in human ADPKD patient-derived cells, reducing cyst expansion.
Conclusions:
- CD peptide-functionalized micelles enable cell-type-selective RNA interference in the kidney.
- Simultaneous suppression of TMEM16A and MCP-1 using targeted siRNA delivery presents a promising therapeutic strategy for ADPKD.
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