Electro-transfer of small interfering RNA ameliorated arthritis in rats

Electro-transfer of small interfering RNA ameliorated arthritis in rats
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DOI:
10.1016/j.bbrc.2005.08.198
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发表时间:
2005-10-28
影响因子:
3.1
通讯作者:
Kubo, T
Kubo, T
中科院分区:
生物学4区
文献类型:
--
作者:
Inoue, A;Takahashi, KA;Kubo, T

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RNA干扰为序列特异性基因沉默提供了强有力的手段。特别是,小干扰RNA(SiRNA)双链可能对治疗人类疾病的分子靶向有用,尽管需要设计新的递送系统来实现有效的和器官特异性的siRNA转导。在本研究中,我们证明了siRNA-多胺复合体的电转移使关节滑膜中高效和特异的基因敲除成为可能。通过这一过程靶向抑制肿瘤坏死因子-α基因可显著改善胶原蛋白诱导的大鼠关节炎。我们的结果提示了用RNA药物治疗类风湿和其他运动性疾病的潜在可行性。Sigma 2005 Elsevier Inc.保留所有权利。
RNA interference provides the powerful means of sequence-specific gene silencing. Particularly, small interfering RNA (siRNA) duplexes may be potentially useful for therapeutic molecular targeting of human diseases, although novel delivery systems should be devised to achieve efficient and organ-specific transduction of siRNA. In the present study, we demonstrated that electro-transfer of a siRNA-polyamine complex made efficient and specific gene knockdown possible in the articular synovium. Targeted suppression of the tumor necrosis factor-alpha gene through this procedure significantly ameliorated collagen-induced arthritis in rats. Our results suggest the potential feasibility of therapeutic intervention with RNA medicines for treatment of rheumatoid and other locomotor diseases. sigma 2005 Elsevier Inc. All rights reserved.