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Mol Ther Nucleic Acids. 2017 Dec 15;9:111-119. doi: 10.1016/j.omtn.2017.09.001. Epub 2017 Sep 12.

Anti-tumor Activity of miniPEG-γ-Modified PNAs to Inhibit MicroRNA-210 for Cancer Therapy.

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Department of Therapeutic Radiology, Yale University, New Haven, CT 06510, USA.
Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA.
Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, USA.
Department of Chemistry and Center for Nucleic Acids Science and Technology (CNAST), Carnegie Mellon University, Pittsburgh, PA 15213, USA.
Department of Pathology, Yale University, New Haven, CT 06510, USA.
Department of Therapeutic Radiology, Yale University, New Haven, CT 06510, USA; Department of Genetics, Yale University, New Haven, CT 06510, USA. Electronic address:


MicroRNAs (miRs) are frequently overexpressed in human cancers. In particular, miR-210 is induced in hypoxic cells and acts to orchestrate the adaptation of tumor cells to hypoxia. Silencing oncogenic miRs such as miR-210 may therefore offer a promising approach to anticancer therapy. We have developed a miR-210 inhibition strategy based on a new class of conformationally preorganized antisense γ peptide nucleic acids (γPNAs) that possess vastly superior RNA-binding affinity, improved solubility, and favorable biocompatibility. For cellular delivery, we encapsulated the γPNAs in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). Our results show that γPNAs targeting miR-210 cause significant delay in growth of a human tumor xenograft in mice compared to conventional PNAs. Further, histopathological analyses show considerable necrosis, fibrosis, and reduced cell proliferation in γPNA-treated tumors compared to controls. Overall, our work provides a chemical framework for a novel anti-miR therapeutic approach using γPNAs that should facilitate rational design of agents to potently inhibit oncogenic microRNAs.


PLGA nanoparticles; PNA; anti-miR; cancer; hypoxia; miR-210; miRNA; oncogenic miRs; γPNA

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