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
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.
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.
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.
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