Judo Bio Demonstrates Sustained Kidney-Selective Gene Silencing with Megalin-STRIKER Platform Across Species
核心洞察
Judo Bio (搜索)'s megalin-STRIKER (搜索) oligonucleotide therapeutics achieved approximately 70% target gene knockdown sustained for 2 months in both rodents and non-human primates.
The ligand-siRNA conjugates specifically target proximal tubular epithelial cells (搜索) in the kidney through megalin (搜索) receptor binding, enabling selective gene silencing.
Preclinical data presented at the Oligonucleotide Therapeutics Society meeting demonstrate dose-dependent gene knockdown and provide foundation for therapeutic applications in systemic and renal diseases (搜索).
Judo Bio (搜索) has demonstrated sustained, kidney-selective gene silencing across multiple species with its megalin-STRIKER (搜索) oligonucleotide therapeutics platform, achieving approximately 70% target gene knockdown that persisted for 2 months following single administration. The preclinical data, presented at the 21st Annual Meeting of the Oligonucleotide Therapeutics Society in Budapest, Hungary, show successful translation of the technology from rodents to non-human primates.
Platform Technology and Mechanism
Megalin (搜索)-STRIKERs are ligand-siRNA conjugates that bind specifically to megalin receptors on proximal tubular epithelial cells (搜索) (PTECs) in the kidney. This receptor-mediated uptake mechanism results in cell-specific delivery of oligonucleotides and subsequent gene silencing of target mRNA. The PTECs play a pivotal role in solute reabsorption and homeostasis, making them strategic targets for therapeutic intervention.
"We are pleased to share the steady progress that we have made in advancing the STRIKE platform for delivery of oligonucleotide therapeutics to the kidney," said Alfica Sehgal, PhD, Chief Scientific Officer of Judo Bio (搜索). "Our results demonstrated dose-dependent gene knockdown exceeding 70% with sustained duration. The modularity of our platform enables a rapid path towards therapeutic application of megalin (搜索)-STRIKERs across multiple systemic diseases (搜索)."
Key Preclinical Findings
The data presented at OTS revealed several critical performance characteristics of the megalin-STRIKER (搜索) platform:
Megalin (搜索)-STRIKERs distributed specifically to PTECs in kidneys across both rodent and non-human primate species, demonstrating cross-species selectivity. In both species, single administration achieved approximately 70% target gene knockdown that was sustained for 2 months, indicating durability of the therapeutic effect.
In rodent studies, the kidney-selective knockdown of the target gene was dose-dependent and corresponded with a dose proportional increase in siRNA levels, providing evidence for the platform's pharmacological predictability.
Therapeutic Applications and Pipeline
Judo Bio (搜索)'s STRIKE (Selectively Targeting RNA Into KidnEy) platform uses a proprietary approach to create ligand-RNA conjugate drugs designed for receptor-mediated uptake by specific kidney cell types. The company's initial pipeline programs focus on megalin (搜索)-STRIKERs that target the megalin receptor family to selectively deliver siRNA therapeutics to the proximal tubule of the kidney.
These therapeutics are designed to silence mRNA expression of specific solute carrier proteins (搜索) (SLCs), thereby inhibiting the uptake of circulating solutes linked to systemic diseases (搜索). The platform's modularity allows for targeting multiple disease-modifying genes expressed in PTECs, potentially opening new therapeutic avenues for both systemic and renal diseases (搜索).
The data provide a foundation for applying megalin (搜索)-STRIKERs to achieve selective gene silencing for therapeutic intervention across a range of conditions where kidney-mediated solute handling plays a role in disease pathogenesis.