Chemotherapy Research Today is a free monthly online journal that collates and summarizes the latest research about Chemotherapy, including details on cancer treatment, side effects, drugs.

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

Peer D, Park EJ, Morishita Y, Carman CV, Shimaoka M

Immune Disease Institute and Department of Anesthesia, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.

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.

Published 1 February 2008 in Science, 319(5863): 627-30.
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