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Intracellular mRNA regulation with self-assembled locked nucleic acid polymer nanoparticles.


ABSTRACT: We present an untemplated, single-component antisense oligonucleotide delivery system capable of regulating mRNA abundance in live human cells. While most approaches to nucleic acid delivery rely on secondary carriers and complex multicomponent charge-neutralizing formulations, we demonstrate efficient delivery using a simple locked nucleic acid (LNA)-polymer conjugate that assembles into spherical micellar nanoparticles displaying a dense shell of nucleic acid at the surface. Cellular uptake of soft LNA nanoparticles occurs rapidly within minutes as evidenced by flow cytometry and fluorescence microscopy. Importantly, these LNA nanoparticles knockdown survivin mRNA, an established target for cancer therapy, in a sequence-specific fashion as analyzed by RT-PCR.

SUBMITTER: Rush AM 

PROVIDER: S-EPMC4046771 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Intracellular mRNA regulation with self-assembled locked nucleic acid polymer nanoparticles.

Rush Anthony M AM   Nelles David A DA   Blum Angela P AP   Barnhill Sarah A SA   Tatro Erick T ET   Yeo Gene W GW   Gianneschi Nathan C NC  

Journal of the American Chemical Society 20140514 21


We present an untemplated, single-component antisense oligonucleotide delivery system capable of regulating mRNA abundance in live human cells. While most approaches to nucleic acid delivery rely on secondary carriers and complex multicomponent charge-neutralizing formulations, we demonstrate efficient delivery using a simple locked nucleic acid (LNA)-polymer conjugate that assembles into spherical micellar nanoparticles displaying a dense shell of nucleic acid at the surface. Cellular uptake of  ...[more]

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