Peptide-conjugated antisense oligonucleotides for targeted inhibition of a transcriptional regulator in vivo.

Peptide-conjugated antisense oligonucleotides for targeted inhibition of a transcriptional regulator in vivo. Research Abstract Details 

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Peptide-conjugated antisense oligonucleotides for targeted inhibition of a transcriptional regulator in vivo. Abstract Text:

Erik Henke,Jonathan Perk,Jelena Vider,Paola de Candia,Yvette Chin,David B Solit,Vladimir Ponomarev,Luca Cartegni,Katia Manova,Neal Rosen,Robert Benezra,Erik Henke,Jonathan Perk,Jelena Vider,Paola de Candia,Yvette Chin,David B Solit,Vladimir Ponomarev,Luca Cartegni,Katia Manova,Neal Rosen,Robert Benezra,Erik Henke,Jonathan Perk,Jelena Vider,Paola de Candia,Yvette Chin,David B Solit,Vladimir Ponomarev,Luca Cartegni,Katia Manova,Neal Rosen,Robert Benezra,

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.

Peptide-conjugated antisense oligonucleotides for targeted inhibition of a transcriptional regulator in vivo. Publishing Authors By Initials

E Henke,J Perk,J Vider,P de Candia,Y Chin,DB Solit,V Ponomarev,L Cartegni,K Manova,N Rosen,R Benezra,E Henke,J Perk,J Vider,P de Candia,Y Chin,DB Solit,V Ponomarev,L Cartegni,K Manova,N Rosen,R Benezra,E Henke,J Perk,J Vider,P de Candia,Y Chin,DB Solit,V Ponomarev,L Cartegni,K Manova,N Rosen,R Benezra,

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Peptide-conjugated antisense oligonucleotides for targeted inhibition of a transcriptional regulator in vivo. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Nature biotechnology

VOLUME: 26

Page Numbers: 91-100

Journal Abbreviation: Nat. Biotechnol.

ISSN: 1087-0156

DAY: 6

MONTH: 01

YEAR: 2008

Peptide-conjugated antisense oligonucleotides for targeted inhibition of a transcriptional regulator in vivo. Information

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LANGUAGE: eng

NlmUniqueID: 9604648

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Grant and Affiliation Information for Peptide-conjugated antisense oligonucleotides for targeted inhibition of a transcriptional regulator in vivo.

AFFILIATION: Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, 1270 York Ave., New York, New York 10021, USA.

Country: United States

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MEDLINETA: Nat Biotechnol

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