Abstract: TH-PO0778
The STRIKE Platform Enables Cross-Species siRNA Delivery and Gene Silencing in the Kidney Proximal Tubules
Session Information
- CKM Axis: Vascular Dysfunction, Atherosclerosis, and Heart Failure in Kidney Diseases
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Cardiovascular-Kidney-Metabolic Health
- 601 Cardiovascular-Kidney-Metabolic Health: Basic
Authors
- Ding, Shiying, Judo Bio, Cambridge, Massachusetts, United States
- Jung, Yun Joon, Judo Bio, Cambridge, Massachusetts, United States
- Lo, Justin, Judo Bio, Cambridge, Massachusetts, United States
- Difazio, Julia, Judo Bio, Cambridge, Massachusetts, United States
- Cunniff, Jeremy, Judo Bio, Cambridge, Massachusetts, United States
- Kleinberg, Nicole, Judo Bio, Cambridge, Massachusetts, United States
- Kozub, Olivia M., Judo Bio, Cambridge, Massachusetts, United States
- Belanger, Adam, Judo Bio, Cambridge, Massachusetts, United States
- Wang, Walter, Judo Bio, Cambridge, Massachusetts, United States
- Ge, Huanying Gary, Judo Bio, Cambridge, Massachusetts, United States
- Zhang, Hongmei, Judo Bio, Cambridge, Massachusetts, United States
- Comer, Eamon Joseph, Judo Bio, Cambridge, Massachusetts, United States
- Lawrence, Jonathan F., Judo Bio, Cambridge, Massachusetts, United States
- Patel, Mayur R., Judo Bio, Cambridge, Massachusetts, United States
- Soundar, Mangala, Judo Bio, Cambridge, Massachusetts, United States
- Sehgal, Alfica, Judo Bio, Cambridge, Massachusetts, United States
Background
Oligonucleotide-based therapeutics have shown broad potential to modulate disease-relevant genes across diverse tissues; however, their application in the kidney has been limited by challenges in targeted and functional delivery. Proximal tubular epithelial cells (PTECs), essential for solute reabsorption and systemic homeostasis, represent a compelling therapeutic cell population for renal and systemic diseases. Judo Bio's proprietary STRIKE (Selectively Targeting RNA Into KidnEy) platform enables megalin-mediated delivery of ligand-conjugated small interfering RNAs to PTECs, achieving efficient, durable gene silencing in this key renal cell type.
Methods
Megalin-binding ligand-siRNA conjugates (STRIKERs) were designed and optimized in vitro and in vivo, with broad assessment of delivery, biodistribution, pharmacodynamic activity and safety in mice and non-human primates (NHPs). siRNA exposure and cellular localization were assessed by fluorescence imaging, mass spectrometry, and in situ hybridization. Target knockdown and functional effects were assessed by qPCR, RNA sequencing, protein analyses, and bioanalytical measurements. Repeat dosing, dual-targeting siRNA strategies, and synergy with small-molecule approaches were also evaluated.
Results
STRIKER-mediated potent knockdown of multiple genes was observed in mice and NHPs, supporting platform modularity and cross-species translation. A single subcutaneous dose produced kidney-specific, dose-dependent and durable gene silencing, with minimal effects in non-renal tissues. Biodistribution confirmed preferential siRNA accumulation in megalin-positive PTECs. STRIKERs targeting solute transporters drove robust mRNA and protein reduction, with corresponding solute changes in mice and NHPs. Repeat dosing resulted in additive knockdown. Platform expansion into dual-targeting STRIKERs enabled simultaneous silencing of multiple transcripts with activity comparable to single-targeting conjugates and stronger functional effects. STRIKERs were well tolerated in rodents and NHPs.
Conclusion
Judo Bio's STRIKE platform harnesses megalin-mediated uptake to selectively deliver siRNA to PTECs, driving potent, durable, kidney-specific gene silencing with cell-type precision. Together, these findings establish a strong foundation for advancing RNA therapeutics for renal and systemic diseases.