Sirnaomics Ltd., a leading biopharmaceutical company in discovery and development of RNAi therapeutics, announced that the Company has developed a Peptide Docking Vehicle (PDoV™) to achieve a peptide-enhanced GalNAc platform for siRNA drug delivery.
Sirnaomics’ GalNAc platform takes advantage of a PDoV™ design that leverages selected small peptides which do not only possess an active endosomal escape property, but also provide two binding sites for the conjugation of dual-siRNA inhibitors. In cell culture and animal models, the PDoV-GalNAc platform has accelerated targeted gene knockdown more rapidly than with GalNAc alone, which is attributed to the rapid endosomal escape afforded by PDoV. In such studies, the maximal knockdown of the targeted gene occurred in the first week with the PDoV-GalNAc as compared to the third week with GalNAc alone.
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The PDoV-GalNAc delivery technology can be effectively adapted for a dual-targeted siRNA therapeutic with different siRNAs, while targeting either two regions of the same mRNA or different mRNAs (of two drug targets). The dual-targeted PDoV-GalNAc siRNA construct has demonstrated an ability to increase the efficiency of targeted gene knockdown by 10 to 15 fold in vitro as compared to a single siRNA construct. Several novel siRNA drug candidates are currently under development using this technology, including STP135G, which targets the hepatocyte-expressed PCSK9 gene for Hypercholesterolemia, STP145G, which targets the viral mRNA for Hepatitis B virus, and STP165G, which targets hepatocyte-expressed Angiotensinogen for Hypertension.
“Sirnaomics has heavily invested in the GalNAc platform because it encompasses a unique design and innovative technology as compared to other platforms currently used for clinical development,” said Dr. Patrick Lu, founder, Chairman of the Board, Executive Director, President and CEO of Sirnaomics. “Based on our PDoV-GalNAc and GalAhead™-delivered siRNA drug candidates that are moving into clinical testing, Sirnaomics is well-positioned to develop new treatments for diseases related to liver hepatocytes. Our GalNAc and Polypeptide Nanoparticle (PNP) delivery technologies provide a solid foundation to serve broad unmet patient needs.”
“Our in vitro and in vivo data has demonstrated the value of our PDoV design in addressing the challenge of improving endosomal escape for treatments developed with GalNAcdelivery,” said Dr. David Evans, Executive Director and Chief Scientific Officer of Sirnaomics. “The PDoV-GalNAc delivery platform not only enhances the benefits of single siRNA therapeutics, but also advances the therapeutic efficacy of dual-targeted siRNA drug candidates. Sirnaomics’ scientific team will continue to advance our novel RNAi therapeutics with development of such cutting-edge technology.”