65 0

Utility of RNAi-mediated prnp gene silencing in neuroblastoma cells permanently infected by prions: Potentials and limitations

Title
Utility of RNAi-mediated prnp gene silencing in neuroblastoma cells permanently infected by prions: Potentials and limitations
Author
류종석
Keywords
Prion; PrP(C); PrP(Sc); RNAi; siRNA; shRNA
Issue Date
2009-11
Publisher
ELSEVIER SCIENCE BV
Citation
ANTIVIRAL RESEARCH, v. 84, No. 2, Page. 185-193
Abstract
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. (C) 2009 Elsevier B.V. All rights reserved.
URI
https://www.sciencedirect.com/science/article/pii/S0166354209004550http://repository.hanyang.ac.kr/handle/20.500.11754/76569
ISSN
0166-3542
DOI
10.1016/j.antiviral.2009.09.002
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE