Down-modulation of cancer targets using locked nucleic acid (LNA)-based antisense oligonucleotides without transfection.

摘要: Usually, small interfering RNAs and most antisense molecules need mechanical or chemical delivery methods to down-modulate the targeted mRNA. However, these approaches complicate interpretations of biological consequences. We show that locked nucleic acid (LNA)-based oligonucleotides (LNA–ONs) readily genes interest in multiple cell lines without any means. The down-modulation was quick, robust, long-lasting specific followed by potent protein. efficiency effect varied among 30 tumor investigated. robust effects were found those cells where nuclear localization LNA–ON clearly observed. Importantly, using agent, we demonstrated HER3 mRNA protein could be efficiently down-modulated a xenograft model. These data provide simple efficient approach identify potential drug targets animal models. Further elucidation mechanism cellular uptake trafficking LNA–ONs may enhance not only therapeutic values this platform but also general.