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  • Title: Lactosylated poly(ethylene glycol)-siRNA conjugate through acid-labile beta-thiopropionate linkage to construct pH-sensitive polyion complex micelles achieving enhanced gene silencing in hepatoma cells.
    Author: Oishi M, Nagasaki Y, Itaka K, Nishiyama N, Kataoka K.
    Journal: J Am Chem Soc; 2005 Feb 16; 127(6):1624-5. PubMed ID: 15700981.
    Abstract:
    The remarkably enhanced gene silencing in hepatoma cells was achieved by assembling lactosylated-PEG-siRNA conjugates bearing acid-labile beta-thiopropionate linkages into polyion complex (PIC) micelles through the mixing with poly(l-lysine). The PIC micelles with clustered lactose moieties on the periphery were successfully transported into hepatoma cells in a receptor-mediated manner, releasing hundreds of active siRNA molecules into the cellular interior responding to the pH decrease in the endosomal compartment. Eventually, almost 100 times enhancement in gene silencing activity compared to that of the free conjugate was achieved for the micelle system, facilitating the practical utility of siRNA therapeutics.
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