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Nanoparticle-based therapy in an in vivo microRNA-155 (miR-155)-dependent mouse model of lymphoma.

MicroRNA-155 (miR-155) is an oncogenic microRNA that regulates several pathways involved in cell division and immunoregulation. It is overexpressed in numerous cancers, is often correlated with poor prognosis, and is thus a key target for future therapies. In this work we show that overexpression of miR-155 in lymphoid tissues results in disseminated lymphoma characterized by a clonal, transplantable pre-B-cell population of neoplastic lymphocytes. Withdrawal of miR-155 in mice with established disease results in rapid regression of lymphadenopathy, in part because of apoptosis of the malignant lymphocytes, demonstrating that these tumors are dependent on miR-155 expression. We show that systemic delivery of antisense peptide nucleic acids encapsulated in unique polymer nanoparticles inhibits miR-155 and slows the growth of these "addicted" pre-B-cell tumors in vivo, suggesting a promising therapeutic option for lymphoma/leukemia.

Pubmed ID: 22685206


  • Babar IA
  • Cheng CJ
  • Booth CJ
  • Liang X
  • Weidhaas JB
  • Saltzman WM
  • Slack FJ


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

June 26, 2012

Associated Grants

  • Agency: NIBIB NIH HHS, Id: R01 EB000487
  • Agency: NHLBI NIH HHS, Id: R01 HL085416

Mesh Terms

  • Animals
  • Apoptosis
  • Base Sequence
  • Blotting, Western
  • DNA Primers
  • Disease Models, Animal
  • Doxycycline
  • Flow Cytometry
  • Lymphoid Tissue
  • Lymphoma
  • Mice
  • MicroRNAs
  • Nanoparticles
  • Polymerase Chain Reaction