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

Genetics

Molecular Biology: Open Access

Author(s): Peer D, Park EJ, Morishita Y, Carman CV, Shimaoka M, Peer D, Park EJ, Morishita Y, Carman CV, Shimaoka M, Peer D, Park EJ, Morishita Y, Carman CV, Shimaoka M, Peer D, Park EJ, Morishita Y, Carman CV, Shimaoka M

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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.
This article was published in Science and referenced in Molecular Biology: Open Access

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