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. 2012 Jan;340(1):109-13.
doi: 10.1124/jpet.111.185884. Epub 2011 Oct 12.

Arthritic joint-targeting small interfering RNA-encapsulated liposome: implication for treatment strategy for rheumatoid arthritis

Yukiko Komano  1 , Nobuhiro Yagi, Ikumi Onoue, Kayoko Kaneko, Nobuyuki Miyasaka, Toshihiro Nanki
Affiliations

Arthritic joint-targeting small interfering RNA-encapsulated liposome: implication for treatment strategy for rheumatoid arthritis

Yukiko Komano et al. J Pharmacol Exp Ther. 2012 Jan.

Abstract

RNA interference, mediated by small interfering RNA (siRNA), is effective in silencing genes with a high degree of specificity. To explore the therapeutic potential of systemically administered siRNA for rheumatoid arthritis (RA), we tested the complex of siRNA and the recently developed wrapsome (siRNA/WS) containing siRNA-encapsulated liposome in mice with collagen-induced arthritis (CIA). Mice with CIA received an intravenous injection of Cy5-labeled siRNA/WS. Fluorescence stereoscopic microscopy and flow cytometry were used to assess the siRNA/WS tissue distribution. The efficacy of siRNA-targeting tumor necrosis factor (TNF)-α/WS in CIA was evaluated by arthritis score. TNF-α mRNA levels in the joints were measured by real-time reverse transcriptase-polymerase chain reaction. The intensity of Cy5 fluorescence was higher in arthritic joints than in nonarthritic sites in Cy5-siRNA/WS-treated mice and remained higher up to 48 h after injection, compared with that in naked Cy5-siRNA-treated mice. Cy5 fluorescence intensity was higher in synovial cells than in splenocytes, bone marrow cells, and peripheral blood leukocytes. The majority of Cy5-positive synovial cells were CD11b⁺ with only a few CD3⁺ cells. Treatment with TNF-α siRNA/WS resulted in significant decreases in severity of arthritis and TNF-α mRNA level in the joints compared with control siRNA/WS. In conclusion, the use of our WS allowed efficient and targeted delivery of siRNAs to arthritic joints. The siRNA/WS was mainly incorporated into CD11b⁺ cells, including macrophages and neutrophils, in the inflamed synovium, suggesting its potential therapeutic effects in RA by silencing the expression of inflammatory molecules produced by these cells.

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