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

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 beta(7) integrin (beta(7) I) were then used to target specific leukocyte subsets involved in gut inflammation. Systemic application of beta(7) 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.

SUBMITTER: Peer D

PROVIDER: S-EPMC2490797 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature

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

Peer Dan D Park Eun Jeong EJ Morishita Yoshiyuki Y Carman Christopher V CV Shimaoka Motomu M

Science (New York, N.Y.) 20080201 5863

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 beta(7) integrin (beta(7) I) were then used to tar ...[more]

PMID: 18239128

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2013-12-31 | GSE43216 | GEO

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