Oligonucleotide therapeutics, such as siRNAs, are clinically validated medicines for use primarily in the liver. Limitations with delivery technology have hampered their use in other tissues, including the kidney. Judo’s foundational insight is to utilize kidney recycling receptors to increase siRNA uptake and activity in specific kidney cell populations.

 

The STRIKE Platform

STRIKE (Selectively Targeting RNA Into KidnEy) is our platform to discover and develop ligand-siRNA conjugates that harness the natural, endogenous process of receptor-mediated endocytosis to deliver oligonucleotide therapeutics selectively to specific kidney cell populations. Our STRIKERs are engineered for optimal delivery efficiency and activity, and can be administered via conventional subcutaneous or intravenous routes.

Judo Bio is pioneering the discovery and development of ligand-siRNA conjugates to achieve gene silencing in specific cells of the kidney to treat systemic and renal diseases.

 

Megalin
A recycling receptor and entry
point for RNA therapeutics

Our first application of the STRIKE platform leverages the megalin receptor family to selectively deliver siRNA therapeutics to the proximal tubule. Megalin is a cell-surface receptor that is highly expressed on proximal tubular epithelial cells (PTECs). It is rapidly internalized, slowly degraded, with high recycling capacity, making it an ideal entry point for intracellular delivery of a ligand-siRNA conjugate.

 

Cell surface
 
Intracellular
Each kidney contains about one million nephrons, the functional unit of the kidney, that together filter about 50 gallons of blood each day. Blood flows through each nephron, beginning at the glomerulus then the proximal tubule on its way out via the collecting duct.

Learn how megalin-STRIKERs reach the PTEC cells from circulation and silence the production of a solute carrier protein to modulate the absorption of solute back into the blood at the proximal tubule.

1
Bind cell Surface receptor

Ligand-siRNA conjugate binds to megalin, an endocytic receptor that is predominantly expressed on the PTEC cells in the proximal tubule of the kidney

1

Learn how megalin-STRIKERs reach the PTEC cells from circulation and silence the production of a solute carrier protein to modulate the absorption of solute back into the blood at the proximal tubule.

2
HARNESS NATURAL ENDOCYTIC PROCESS

Ligand-siRNA is internalized into PTEC cells and released into the cytoplasm for intracellular processing

2

Learn how megalin-STRIKERs reach the PTEC cells from circulation and silence the production of a solute carrier protein to modulate the absorption of solute back into the blood at the proximal tubule.

3
SILENCE THE GENE THAT EXPRESSES THE TARGET SOLUTE CARRIER

siRNA degrades mRNA resulting in reduction of specific solute carrier proteins, thereby decreasing plasma solute concentration

3
 
click through the steps to see how it works

We have rapidly applied our STRIKE platform

to develop a pipeline
of megalin-STRIKERs

our pipeline

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