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GS-10 is a tumor-targeted RNAi therapeutic candidate developed by GeneSegues Therapeutics for the treatment of solid tumors, including head and neck cancer. It consists of a 20 nm crystalline capsule (nanoparticle) that delivers single-stranded RNAi oligonucleotides designed to silence Protein Kinase CK2 (CK2). The nanoparticle is functionalized with tenfibgen, a ligand derived from Tenascin-C, which is frequently overexpressed in the tumor microenvironment and on the surface of various solid tumors. This targeting mechanism allows for the efficient delivery of the RNAi payload to both primary tumors and metastatic sites. By knocking down CK2, a protein kinase involved in cell cycle regulation and anti-apoptotic signaling, GS-10 aims to inhibit tumor growth and progression. Preclinical research has also explored a high-dose priming strategy to elevate RISC complex proteins, such as Ago2, to enhance the efficacy of subsequent RNAi treatments.
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