TY - JOUR
T1 - Systemic leukocyte-directed siRNA delivery revealing cyclin D1 as an anti-inflammatory target
AU - Peer, Dan
AU - Eun, Jeong Park
AU - Morishita, Yoshiyuki
AU - Carman, Christopher V.
AU - Shimaoka, Motomu
N1 - Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2008/2/1
Y1 - 2008/2/1
N2 - 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.
AB - 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.
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U2 - 10.1126/science.1149859
DO - 10.1126/science.1149859
M3 - Article
C2 - 18239128
AN - SCOPUS:38849166053
SN - 0036-8075
VL - 319
SP - 627
EP - 630
JO - Science
JF - Science
IS - 5863
ER -