Chinese Bulletin of Life Sciences RNA RNA. Progress in RNA interference therapeutics. CHU Liang 1, LIU Xinyuan 1,2 *

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1 Chinese Bulletin of Life Sciences Vol. 19, No. 2 Apr., (2007) RNA RNA RNA RNA RNA RNA RNA(siRNA) RNA(shRNA) RNA RNA RNA RNA R A Progress in RNA interference therapeutics CHU Liang 1, LIU Xinyuan 1,2 * (1 Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai , China; 2 Xinyuan Institute of Medicine and Biotechnology, Zhejiang Sci-Tech University, Hangzhou , China) Abstract: RNA interference (RNAi) is a conserved biologic response to double-stranded RNA that resulted in the sequence-specific silencing of target gene expression. RNAi is a valuable tool in the treatment of diseases for its potency to silence disease-associated genes in tissue culture and animal models. RNAi can be induced in mammalian cells by the introduction of chemically synthesized small interfering RNAs (sirnas) or by plasmid and viral vectors that express short-hairpin RNAs (shrnas) that can be processed to sirnas by the cellular machinery. In this review, we focus on the potential therapeutic use of RNAi. Also reviewed, are the challenges involved in developing RNAi for clinical use. Key words: RNA interference; small interfering RNA; short-hairpin RNA; gene silence RNA (RNA interference, RNAi) RNA RNA(small interfering RNA, sirna); RNA (short-hairpin RNA, shrna) RNA RNA 1 RNA 1.1 RNA (KSCX2-YW-R-09) (1980 ) (1927 ) * Tel: xyliu@sibs.ac.cn

2 118 RNA Giladi [1] sirna HBV mrna DNA Chen SARS RNA sirna SARS [2] sirna RNA HIV sirna HIV chemokine (C-C motif) receptor 5 (CCR5) [3] [4] RNA 1.2 RNA Bcl-2 survivin EGFR VEGF [5] RNA RNA RAS 85% 40% RAS K-RAS H-RAS N-RAS RAS Brummelkamp [6] shrna RNA K-RAS V12 RAS K-RAS V RNA CXCR4 CXCR4 RNA CXCR4 [7-9] VEGF VEGF sirna (atelocollagen) [10-11] RNA 30% MDR1 RNA MDR1 [12] Bcl-2 etopodise daunorubicin [13] sirna RNA 1.3 TNFα TNFα Schiffelers [14] TNFα sirna 1.4

3 RNA 119 Acuity pharmaceuticals Bevasiranib VEGF sirna VEGF 129 Bevasiranib Bevasiranib VEGF Bevasiranib Shao [15] sirna NCI-H292 TGFα GFR sirna Syk Ulanova [16] Syk β1-integrin RNA Gou [17] shrna II 2 RNA Acuity pharmaceuticals Bevasiranib Sirna therapeutics Sirna-027 Sirna-027 VEGF sirna (26 100%) 8w 5 (19%) 12w 24 (92%) 4 (15%) Sirna-AV34 Alnylam pharmaceuticals ALN-RSV01 RNA (respiratory syncytial virus, RSV) RNA N 3 RNA 3.1 RNA RNA sirna shrna DNA shrna DNA shrna [18-22] RNA RNA [23-26] RNA [27-29] [30] 3.2 RNA RNA mrna sirna mrna sirna RNA [31-33] Nature 8 shrna shrna shrna RNA shrna RNA(microRNA mirna) RNA exportin 5 mirna [34]

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