Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.


Arthritic Joint-Targeting siRNA/Wrapsome as a Treatment Strategy for Rheumatoid Arthritis

Komano1,  Yukiko, Yagi2,  Nobuhiro, Onoue1,  Ikumi, Kaneko1,  Kayoko, Miyasaka1,  Nobuyuki, Nanki1,  Toshihiro

Tokyo Medical and Dental University. Tokyo, Japan
Kyowa Hakko Kirin Co., Ltd.

Purpose:

To explore the therapeutic potential of systemically administered small interfering RNAs encapsulated with Wrapsome® (siRNA/WS) for rheumatoid arthritis (RA), which contains siRNA in a core that is fully enveloped by a neutral lipid bilayer.

Method:

Tissue distributions of fluorescence (Cy5)-labeled siRNA/WS or naked Cy5-labeled siRNA injected intravenously into collagen-induced arthritis (CIA) mice were assessed by fluorescence stereoscopic microscope and flow cytometry. Efficacy of siRNA targeting TNF-a/WS for CIA was evaluated with arthritis scoring system, and levels of TNF-a mRNA in joints were measured using real-time RT-PCR assay.

Results:

Observation with stereoscopic microscope showed that levels of Cy5 was more intense in arthritic joints than in non-arthritic sites in mice treated with Cy5-siRNA/WS, and remained highly intense up to 48 hrs post-injection. On the contrary, the levels of Cy5 in arthritic joints in mice treated with naked Cy5-siRNA rapidly diminished. Cells in the synovium showed the highest intensity of Cy5 in those tested including spleen, peripheral blood, lung, and bone marrow. Most of the Cy5-positive cells in the synovium were monocytes/macrophages (CD11b+ or F4/80+), whereas, there were a few Cy5-positive lymphocytes. Mice treated with TNF-a siRNA/WS showed decreased severity of arthritis compared with control siRNA/WS. The Levels of TNF-a mRNA in the joints of mice treated with TNF-a siRNA/WS were significantly lower than those in controls.

Conclusion:

Using the Wrapsome®, efficient and targeted delivery of siRNAs to arthritic joints was achieved. The siRNA/WS were incorporated into monocytes/macrophages in the inflamed synovium, indicating that it could be a therapeutic tool to silence expressions of inflammatory cytokines produced by those cells in situ.

To cite this abstract, please use the following information:
Komano, Yukiko, Yagi, Nobuhiro, Onoue, Ikumi, Kaneko, Kayoko, Miyasaka, Nobuyuki, Nanki, Toshihiro; Arthritic Joint-Targeting siRNA/Wrapsome as a Treatment Strategy for Rheumatoid Arthritis [abstract]. Arthritis Rheum 2009;60 Suppl 10 :22
DOI: 10.1002/art.25105

Abstract Supplement

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