Design and Validation of siRNA Targeting Gankyrin in the Murine Liver

Autor: Tatiana O. Abakumova, Tatiana Prikazchikova, Olga V. Sergeeva, Timofei S. Zatsepin
Rok vydání: 2021
Předmět:
Zdroj: Russian Journal of Bioorganic Chemistry. 47:441-446
ISSN: 1608-330X
1068-1620
DOI: 10.1134/s1068162021020229
Popis: Despite recent success in the treatment of hepatocellular carcinoma and other liver cancers, development of new therapeutic approaches remains an unmet medical need. The application of therapeutic nucleic acids allows suppression of complex targets over the long term. Nucleic acid therapeutics can be used either independently or in combination with small molecules and antibodies. Here, we performed design, synthesis and validation of siRNAs targeting gankyrin mRNA in vitro and in vivo. As gankyrin upregulation in hepatocellular carcinoma causes increased proliferation of hepatocytes, gankyrin is a promising therapeutic target. We have shown that the most effective miRNAs are complementary to mRNA fragments that form both single-and double-stranded regions as predicted by modeling of the gankyrin mRNA secondary structure. The most efficient siRNAs were formulated in lipid nanoparticles and showed downregulation of gankyrin mRNA in the murine liver of more than 90% after a single injection of 0.2 mg/kg. Selected siRNAs can be used to study the role of gankyrin in the development of liver cancer and metabolic diseases in murine models.
Databáze: OpenAIRE
Externí odkaz: