Systemic leukocyte-directed siRNA delivery revealing cyclin D1 as an anti-inflammatory target

Dan Peer, Jeong Park Eun, Yoshiyuki Morishita, Christopher V. Carman, Motomu Shimaoka

Research output: Contribution to journalArticle

409 Scopus citations

Abstract

Cyclin D1 (CyD1) is a pivotal cell cycle-regulatory molecule and a well-studied therapeutic target for cancer. Although CyD1 is also strongly up-regulated at sites of inflammation, its exact roles in this context remain uncharacterized. To address this question, we developed a strategy for selectively silencing CyD1 in leukocytes in vivo. Targeted stabilized nanoparticles (tsNPs) were loaded with CyD1-small interfering RNA (siRNA). Antibodies to β7 integrin (β7 I) were then used to target specific leukocyte subsets involved in gut inflammation. Systemic application of β7 I-tsNPs silenced CyD1 in leukocytes and reversed experimentally induced colitis in mice by suppressing leukocyte proliferation and T helper cell 1 cytokine expression. This study reveals CyD1 to be a potential anti-inflammatory target, and suggests that the application of similar modes of targeting by siRNA may be feasible in other therapeutic settings.

Original languageEnglish (US)
Pages (from-to)627-630
Number of pages4
JournalScience
Volume319
Issue number5863
DOIs
StatePublished - Feb 1 2008

ASJC Scopus subject areas

  • General

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