Utility of Customized PEG Linkers for the delivery of oligonucleotides without the use of transfection agents
نویسندگان
چکیده
RNA antagonists using locked nucleic acid (LNA) antisense oligonucleotides are among the most promising therapeutics to treat cancer. Unlike the other antisense oligonucleotides, LNA-based oligonucleotides have high target binding affinity and long tissue stability. LNA can inhibit the mRNA expression at nanomolar and subnanomolar concentrations in the presence of lipofectamine. However, systemic delivery of LNA is still a challenge. Using our Customized PEG linkers we achieved in vitro mRNA down-modulation in the absence of transfection agents in a dose dependent manner. By attaching targeting moieties to these PEG linkers, cell specific binding and internalization were observed in fluorescence microscopy studies. Preclinical xenograft models were used to study the bio-distribution and tumor accumulation of PEG-LNA conjugates.
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