Small Interfering RNA-Induced Transcriptional Gene Silencing in Human Cells

Science ◽  
2004 ◽  
Vol 305 (5688) ◽  
pp. 1289-1292 ◽  
Author(s):  
K. V. Morris
2008 ◽  
Vol 89 (9) ◽  
pp. 2349-2358 ◽  
Author(s):  
Chunying Meng ◽  
Jun Chen ◽  
Shou-wei Ding ◽  
Jinrong Peng ◽  
Sek-Man Wong

Many plant and animal viruses have evolved suppressor proteins to block host RNA silencing at various stages of the RNA silencing pathways. Hibiscus chlorotic ringspot virus (HCRSV) coat protein (CP) is capable of suppressing the transiently expressed sense-RNA-induced post-transcriptional gene silencing (PTGS) in Nicotiana benthamiana. Here, constitutively expressed HCRSV CP from transgenic Arabidopsis was found to be able to rescue expression of the silenced GUS transgene. The HCRSV CP-transgenic Arabidopsis (line CP6) displayed several developmental abnormalities: elongated, downwardly curled leaves and a lack of coordination between stamen and carpel, resulting in reduced seed set. These abnormalities are similar to those observed in mutations of the genes of Arabidopsis RNA-dependent polymerase 6 (rdr6), suppressor of gene silencing 3 (sgs3), ZIPPY (zip) and dicer-like 4 (dcl4). The accumulation of microRNA (miRNA) miR173 remained stable; however, the downstream trans-acting small interfering RNA (ta-siRNA) siR255 was greatly reduced. Real-time PCR analysis showed that expression of the ta-siRNA-targeted At4g29770, At5g18040, PPR and ARF3 genes increased significantly, especially in the inflorescences. Genetic crossing of CP6 with an amplicon-silenced line (containing a potato virus X–green fluorescent protein transgene under the control of the 35S cauliflower mosaic virus promoter) suggested that HCRSV CP probably interfered with gene silencing at a step after RDR6. The reduced accumulation of ta-siRNA might result from the interference of HCRSV CP with Dicer-like protein(s), responsible for the generation of dsRNA in ta-siRNA biogenesis.


2004 ◽  
Vol 5 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Bentham Science Publisher Zhang J. ◽  
Bentham Science Publisher Hua Z.C.

2018 ◽  
Vol 65 (3) ◽  
pp. 400-410 ◽  
Author(s):  
Ying-qin Li ◽  
Fa-huan Song ◽  
Ke Zhong ◽  
Guang-yin Yu ◽  
Prince Last Mudenda Zilundu ◽  
...  

2020 ◽  
Vol 184 (2) ◽  
pp. 647-657 ◽  
Author(s):  
Steven H. Schwartz ◽  
Bill Hendrix ◽  
Paul Hoffer ◽  
Rick A. Sanders ◽  
Wei Zheng

2020 ◽  
Vol 6 (30) ◽  
pp. eaba5379 ◽  
Author(s):  
Md. Nazir Hossen ◽  
Lin Wang ◽  
Harisha R. Chinthalapally ◽  
Joe D. Robertson ◽  
Kar-Ming Fung ◽  
...  

Gene silencing using small-interfering RNA (siRNA) is a viable therapeutic approach; however, the lack of effective delivery systems limits its clinical translation. Herein, we doped conventional siRNA-liposomal formulations with gold nanoparticles to create “auroliposomes,” which significantly enhanced gene silencing. We targeted MICU1, a novel glycolytic switch in ovarian cancer, and delivered MICU1-siRNA using three delivery systems—commercial transfection agents, conventional liposomes, and auroliposomes. Low-dose siRNA via transfection or conventional liposomes was ineffective for MICU1 silencing; however, in auroliposomes, the same dose gave >85% gene silencing. Efficacy was evident from both in vitro growth assays of ovarian cancer cells and in vivo tumor growth in human ovarian cell line—and patient-derived xenograft models. Incorporation of gold nanoparticles shifted intracellular uptake pathways such that liposomes avoided degradation within lysosomes. Auroliposomes were nontoxic to vital organs. Therefore, auroliposomes represent a novel siRNA delivery system with superior efficacy for multiple therapeutic applications.


2005 ◽  
Vol 65 (13) ◽  
pp. 5544-5553 ◽  
Author(s):  
Ying Zhang ◽  
Chang U.K. Lim ◽  
Eli S. Williams ◽  
Junqing Zhou ◽  
Qinming Zhang ◽  
...  

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