Systemic delivery of siRNA down regulates brain prion protein and ameliorates neuropathology in prion disorder

PLoS One. 2014 Feb 14;9(2):e88797. doi: 10.1371/journal.pone.0088797. eCollection 2014.


One of the main challenges for neurodegenerative disorders that are principally incurable is the development of new therapeutic strategies, which raises important medical, scientific and societal issues. Creutzfeldt-Jakob diseases are rare neurodegenerative fatal disorders which today remain incurable. The objective of this study was to evaluate the efficacy of the down-regulation of the prion protein (PrP) expression using siRNA delivered by, a water-in-oil microemulsion, as a therapeutic candidate in a preclinical study. After 12 days rectal mucosa administration of Aonys/PrP-siRNA in mice, we observed a decrease of about 28% of the brain PrP(C) level. The effect of Aonys/PrP-siRNA was then evaluated on prion infected mice. Several mice presented a delay in the incubation and survival time compared to the control groups and a significant impact was observed on astrocyte reaction and neuronal survival in the PrP-siRNA treated groups. These results suggest that a new therapeutic scheme based an innovative delivery system of PrP-siRNA can be envisioned in prion disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Brain / pathology*
  • Cell Count
  • Cytokines / biosynthesis
  • Down-Regulation*
  • Female
  • Gene Transfer Techniques*
  • Immunohistochemistry
  • Mice
  • Mice, Inbred C57BL
  • PrPC Proteins / metabolism*
  • PrPSc Proteins / metabolism
  • Prion Diseases / metabolism
  • Prion Diseases / pathology*
  • RNA, Small Interfering / metabolism*
  • Survival Analysis
  • Time Factors
  • Vacuoles / metabolism


  • Cytokines
  • PrPC Proteins
  • PrPSc Proteins
  • RNA, Small Interfering

Grant support

This work was supported by Medesis Pharma. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.