megalin-STRIKERs

Megalin-STRIKERs are proprietary **ligand-siRNA conjugates** developed by Judo Bio that harness the megalin receptor for targeted delivery of oligonucleotide therapeutics to the kidney[2][3]. The technology uses the STRIKE (Selectively Targeting RNA Into KidnEy) platform to deliver siRNA therapeutics specifically to **proximal tubular epithelial cells (PTECs)** in the kidney through receptor-mediated endocytosis[2][3][4]. The mechanism involves binding of the megalin-targeting ligand to megalin receptors, which are highly expressed on PTECs. Upon binding, the conjugate is internalized into the cells, where the siRNA is released into the cytoplasm for intracellular processing[3]. The siRNA then binds to target mRNA and induces its degradation, leading to gene silencing[1][3]. The platform's initial focus is on silencing **solute carrier proteins (SLCs)** to modulate solute absorption and manage systemic diseases such as **type II diabetes and hypertension**[1][2][4]. Preclinical studies demonstrated approximately **70% target gene knockdown sustained for 2 months** following a single administration in both rodents and non-human primates[2][4]. The technology shows kidney-specific distribution with no gene knockdown observed in other tissues, including the liver[1].

Other names

STRIKERSTRIKERs