Robust Gene Silencing Achieved with Megalin-STRIKERs in Rodents and Non-Human Primates

Strategic Insights -

Researchers at Judo Bio have made significant progress in developing oligonucleotide medicines that target specific gene expression in the kidney. Their megalin-STRIKERs demonstrate robust and durable gene silencing in rodents and non-human primates, opening up new possibilities for therapeutic intervention in systemic and renal diseases. By binding to megalin on proximal tubular epithelial cells (PTECs) in the kidney, megalin-STRIKERs achieve cell-specific uptake of oligonucleotide and subsequent gene silencing of the target mRNA.

Key Takeaways:

  • Megalin-STRIKERs, a type of ligand-siRNA conjugate, successfully target gene expression in PTECs in the kidney, achieving sustained gene silencing across multiple targets.
  • Preclinical data demonstrate that megalin-STRIKERs achieve over 70% target gene knockdown in rodents and non-human primates, sustained for up to 2 months with a single administration.
  • The modularity of the STRIKE platform enables rapid development of megalin-STRIKERs for various systemic diseases, with a focus on silencing disease-modifying genes.
  • Dr. Alfica Sehgal, Chief Scientific Officer at Judo Bio, highlights the significance of the results, stating that the platform's therapeutic potential enables a rapid path towards therapeutic application.
  • Megalin-STRIKERs show promise in inhibiting the uptake of circulating solutes linked to systemic diseases, making them a potential solution for various health conditions.

Statistics:

  • 70% target gene knockdown achieved in both rodents and non-human primates.
  • 2 months of sustained gene silencing observed with a single administration of megalin-STRIKERs.
  • Kidney-selective knockdown of target gene in rodents is dose-dependent, corresponding with a proportional increase in siRNA levels.

Sources:

  • Judo Bio, "Judo Bio Announces Presentation of Preclinical Data Demonstrating Robust and Sustained Gene Silencing with Megalin-STRIKER Oligonucleotide Therapeutics"
  • Oligonucleotide Therapeutics Society (OTS), "21st Annual Meeting"
  • Judo Bio website, " Megalin-STRIKERs for Systemic and Renal Diseases"