5\'-triphosphate-siRNA: turning gene silencing and Rig-I activation against melanoma (Nat Med, 2008, 11:1256-1263)

報告日期: 2009/04/10
報告時間: 16:00/16:50
報告學生: 林君杰
講評老師: 林秋烽
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/980410-2.pdf

5’-triphosphate-siRNA: turning gene silencing and Rig-I activation against melanoma

Hendrik Poeck, Robert Besch, Cornelius Maihoefer, Marcel Renn, Damia Tormo, Svetlana Shulga Morskaya, Susanne Kirschnek, Evelyn Gaffal, Jennifer Landsberg, Johannes Hellmuth, Andreas Schmidt, David Anz, Michael Bscheider, Tobias Schwerd, Carola Berking, Carole Bourquin, Ulrich Kalinke, Elisabeth Kremmer, Hiroki Kato, Shizuo Akira, Rachel Meyers, Georg Hacker, Michael Neuenhahn, Dirk Busch, Jurgen Ruland, Simon Rothenfusser, Marco Prinz, Veit Hornung, Stefan Endres, Thomas Tuting & Gunther Hartmann

 

NATURE MEDICINE, 14 (11), 2008

 

SpeakerChun-Chieh Lin

CommentatorDr. Chiou-Feng Lin

Date: 10 April, 2008 (16:00~16:50)

Place: Room 602

 

Abstract

  Tumors tend to escape from limited proliferation states to create more suitable growth situation, even these malignances can evade from single-target therapy specifically against tumor antigens. Thus, combinatorial therapy may be a necessary strategy for tumor treatment. Besides RNAi method for inhibiting tumor survival factors such as Bcl21, Rig-I-mediated innate immune responses for detecting 5’-triphosphate single-stranded RNA virus were also applied2. Taken together, the authors have developed a kind of siRNA which contained 5’-triphosphate moiety and the sequence was designed for silencing Bcl2 expression, so called sp-siRNA. The 3p-siRNA exhibited strong Bcl2 silencing activity and induction of apoptosis in B16 melanoma cells. 3p-siRNA also showed potent anti-tumor abilities on reduced metastasis to lungs in mouse model. The machinery of 3p-siRNA on anti-tumor activity was confirmed to inhibit Bcl2 for promoting apoptosis and induce Rig-I for type I IFN production to recruit and activate NK cells near tumor nodules. In addition to diminish melanoma progression, 3p-siRNA could be applied to reduce other kinds of tumor growth. In conclusion, the 3p-siRNA system provides a more efficient anti-tumor therapy from different angles of tumor characteristics.

 

References

1.  Schlee, M., Hornung, V., & Hartmann, G., siRNA and isRNA: two edges of one sword. Mol Ther 14 (4), 463-470 (2006).

2.  Yoneyama, M. & Fujita, T., Function of RIG-I-like receptors in antiviral innate immunity. J Biol Chem 282 (21), 15315-15318 (2007).