کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5823036 | 1117996 | 2009 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Utility of RNAi-mediated prnp gene silencing in neuroblastoma cells permanently infected by prions: Potentials and limitations
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ویروس شناسی
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چکیده انگلیسی
Prion diseases are incurable, transmissible neurodegenerative disorders in humans and animals. Because the disease-associated isoform of prion protein, PrPSc, is conformationally converted from cellular prion protein, PrPC, knockdown of PrPC expression by RNA interference (RNAi) implicates therapy for prion diseases. In this study, introduction of small interfering (si) and small hairpin (sh) RNAs targeting the prion protein gene (prnp) transcripts triggered specific gene silencing and reduced the PrPC level in both prion-free and -infected neuroblastoma cell lines. Furthermore, this approach suppressed PrPSc formation and ultimately eliminated PrPSc from prion-infected cell lines. However, prolonged culture of cured cells resulted in reappearance of PrPSc in the cell population, presumably by de novo PrPSc formation from residual PrPC uncontrolled by RNAi and PrPSc remained under the detection limit. Protein misfolding cyclic amplification assays further confirmed that lysate of cured cells was sufficient to support PrPSc propagation. Our data not only suggest a potential treatment option but also implicate a caveat for using an RNAi approach for prion diseases. These findings provide critical information required to advance RNAi-based prevention and therapy for prion diseases of humans and animals.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Antiviral Research - Volume 84, Issue 2, November 2009, Pages 185-193
Journal: Antiviral Research - Volume 84, Issue 2, November 2009, Pages 185-193
نویسندگان
Younghwan Kim, Boram Han, William Titlow, Charles E. Mays, Moosik Kwon, Chongsuk Ryou,