Phosphorothioate oligonucleotides reduce PrP levels and prion infectivity in cultured cells.

Phosphorothioate oligonucleotides reduce PrP levels and prion infectivity in cultured cells. Research Abstract Details 

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Phosphorothioate oligonucleotides reduce PrP levels and prion infectivity in cultured cells. Abstract Text:

Marcela V Karpuj,Kurt Giles,Sagit Gelibter-Niv,Michael R Scott,Vishwanath R Lingappa,Francis C Szoka,David Peretz,Wilfred Denetclaw,Stanley B Prusiner,

Prions are composed solely of the disease-causing prion protein (PrPSc) that is formed from the cellular isoform PrPC by a posttranslational process. Here we report that short phosphorothioate DNA (PS-DNA) oligonucleotides diminished the levels of both PrPC and PrPSc in prion-infected neuroblastoma (ScN2a) cells. The effect of PS-DNA on PrP levels was independent of the nucleotide sequence. The effective concentration (EC50) of PS-DNA required to achieve half-maximal diminution of PrPSc was approximately 70 nM, whereas the EC50 of PS-DNA for PrPC was more than 50-fold greater. This finding indicated that diminished levels of PrPSc after exposure to PS-DNA are unlikely to be due to decreased PrPC levels. Bioassays in transgenic mice demonstrated a substantial diminution in the prion infectivity after ScN2a cells were exposed to PS-DNAs. Whether PS-DNA will be useful in the treatment of prion disease in people or livestock remains to be established.

Phosphorothioate oligonucleotides reduce PrP levels and prion infectivity in cultured cells. Publishing Authors By Initials

MV Karpuj,K Giles,S Gelibter-Niv,MR Scott,VR Lingappa,FC Szoka,D Peretz,W Denetclaw,SB Prusiner,

For similar cells: cells, cultured: tumor cells, cultured research abstracts see: cells: cells, cultured: tumor cells, cultured research

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Phosphorothioate oligonucleotides reduce PrP levels and prion infectivity in cultured cells. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Molecular medicine (Cambridge, Mass.)

VOLUME: 13

Page Numbers: 190-8

Journal Abbreviation: Mol. Med.

ISSN: 1076-1551

DAY: 3

MONTH: 12

YEAR: 2007

Phosphorothioate oligonucleotides reduce PrP levels and prion infectivity in cultured cells. Information

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LANGUAGE: eng

NlmUniqueID: 9501023

Phosphorothioate oligonucleotides reduce PrP levels and prion infectivity in cultured cells. Keywords Mesh Terms:

KEYWORDS: Tumor Cells, Cultured

MESH TERMS: pathogenicity

Chemical & Substance for Abstract: Phosphorothioate oligonucleotides reduce PrP levels and prion infectivity in cultured cells. Information

Substance Name: phosphorodithioic acid

Registry Number: 15834-33-0

Grant and Affiliation Information for Phosphorothioate oligonucleotides reduce PrP levels and prion infectivity in cultured cells.

AFFILIATION: Institute for Neurodegenerative Diseases and Department of Neurology, University of California, San Francisco, CA 94143-0518, USA.

Country: United States

AGENCY: United States NCI

GRANT: P20 CA091471

ACRONYM: CA

MEDLINETA: Mol Med

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