Prions are composed solely of the disease-causing prion protein (PrP Sc) that is formed from the cellular isoform PrPC by a post-translational 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 ∼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.
CITATION STYLE
Karpuj, M. V., Giles, K., Gelibter-Niv, S., Scott, M. R., Lingappa, V. R., Szoka, F. C., … Prusiner, S. B. (2007). Phosphorothioate oligonucleotides reduce PrPSc levels and prion infectivity in cultured cells. Molecular Medicine, 13(3–4), 190–198. https://doi.org/10.2119/2006-00073.Karpuj
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