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Targeted Delivery of miRNA Antagonists to Myeloid Cells In Vitro and In Vivo

  • Yu-Lin Su
  • Piotr Swiderski
  • Guido Marcucci
  • Marcin KortylewskiEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1974)

Abstract

Elevated levels of microRNAs in cancer cells are often associated with oncogenic effects and thus provide potential therapeutic targets. However, the lack of efficient delivery methods for synthetic miRNA inhibitors, antagomiR, or anti-miR oligonucleotides hindered clinical translation of such strategies. We recently developed an approach for targeted delivery of synthetic, 2′-O-methyl-modified antagomiR molecules to normal and malignant myeloid cells and B cells by tethering to the single-stranded, phosphorothioate oligodeoxynucleotides (PSO). The PSO-antagomiR are rapidly internalized through scavenger receptor-mediated endocytosis by human monocytes, dendritic cells, B cells, as well as myeloid leukemia and B-cell lymphoma cells, but not by T cells. Following internalization, the unformulated PSO-antagomiR potently reduces levels of target miRNA and modulates expression of downstream protein targets, both in vitro and in vivo. The simple design of PSO-antagomiR conjugates enable adaptation of this strategy for targeting oncogenic miRNAs in nonmalignant and malignant myeloid cells and B cells.

Keywords

MicroRNA miRNA Anti-miR AntagomiR Oligonucleotides Myeloid cells Leukemia 

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Yu-Lin Su
    • 1
  • Piotr Swiderski
    • 2
  • Guido Marcucci
    • 3
  • Marcin Kortylewski
    • 1
    Email author
  1. 1.Department of Immuno-OncologyBeckman Research Institute at City of HopeDuarteUSA
  2. 2.Department of Molecular MedicineBeckman Research Institute at City of HopeDuarteUSA
  3. 3.Hematologic MalignanciesBeckman Research Institute at City of HopeDuarteUSA

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