dsVHL-821

dsVHL-821 is a small activating RNA (saRNA) designed to target the promoter region of the Von Hippel-Lindau (VHL) gene. Developed through a collaboration between the Korea Research Institute of Bioscience and Biotechnology (KRIBB) and Ractigen Therapeutics, it utilizes the mechanism of RNA activation (RNAa) to specifically up-regulate VHL expression at both the mRNA and protein levels. In preclinical models of renal cell carcinoma (RCC), dsVHL-821 has demonstrated the ability to inhibit cell growth and induce apoptosis by modulating downstream pathways, including the up-regulation of p53 and the activation of caspase 3/7 and poly-ADP-ribose polymerase (PARP). The drug functions by recruiting Argonaute 2 (Ago2) and RNA polymerase II to the VHL promoter, leading to epigenetic modifications such as increased histone H3K4 dimethylation and H4 acetylation, alongside decreased H3K9 and H3K27 dimethylation.