Peptide-conjugated antisense oligonucleotides for targeted inhibition of a transcriptional regulator in vivo (Nat Biotechnol, 2008, 26:91-100)

報告日期: 2008/05/20
報告時間: 17:10/18:00
報告學生: 莊智弘
講評老師: 吳昭良
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/970520-3.pdf

Peptide-conjugated antisense oligonucleotides for targeted

inhibition of a transcriptional regulator in vivo

Henke E, Perk J, Vider J, de Candia P, Chin Y, Solit DB, Ponomarev V, Cartegni L, Manova K, Rosen N, Benezra R. Nat Biotechnol. 2008 Jan; 26:91-100

 

Speaker: Chuang Chih-Hing (莊智弘)

Commentator: Wu, Chao-Liang (吳昭良老師)

Date: 2008/05/20 17:00-17:50

Place Room: 602

 

Abstract:

Transcription factors are important targets for the treatment of a variety of malignancies but are extremely difficult to inhibit, as they are located in the cell’s nucleus and act mainly by protein-DNA and protein-protein interactions. The transcriptional regulators Id1 and Id3 are attractive targets for cancer therapy as they are required for tumor invasiveness, metastasis and angiogenesis. We report here the development of an antitumor agent that downregulates Id1 effectively in tumor endothelial cells in vivo. Efficient delivery and substantial reduction of Id1 protein levels in the tumor endothelium were effected by fusing an antisense molecule to a peptide known to home specifically to tumor neovessels. In two different tumor models, systemic delivery of this drug led to enhanced hemorrhage, hypoxia and inhibition of primary tumor growth and metastasis, similar to what is observed in Id1 knockout mice. Combination with the Hsp90 inhibitor 17 - (allylamino) - 17- demethoxygeldanamycin yielded virtually complete growth suppression of aggressive breast tumors.

 

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