A Rapid Ultrasensitive Assay for Detecting Prions Based on the Seeded Polymerization of Recombinant Normal Prion Protein (rPrP-sen)


Prion diseases are neurodegenerative diseases of great public concern as humans may either develop disease spontaneously or, more rarely, due to mutations in their prion protein gene or exposures to external sources of infection. Prion disease is caused by the accumulation in the nervous system of abnormal aggregates of prion protein. This technology enables rapid, economical, and ultrasensitive detection of disease-associated forms of prion protein. Specifically, prion aggregates (contained in a biological sample) seed the polymerization of recombinant, monomeric prion protein (rPrP-sen) and the polymerized product is detected as a highly amplified indicator of infectious prions in the sample. This assay differs from the protein-misfolding cyclic amplification assay (PMCA) because it enables the effective use of bacterially expressed rPrP-sen and does not require multiple amplification rounds. In its current embodiment, this assay can be used to detect prions in tissues or fluids from humans (Creutzfeldt-Jakob disease (CJD)), sheep (scrapie), cattle (bovine spongiform encephalopathy), and deer (chronic wasting disease (CWD)). For example, analyses of cerebrospinal fluid and/or nasal brushings from living sporadic CJD patients has allowed for nearly 100% accurate diagnosis.

This technology is available for licensing for commercial development in accordance with 35 U.S.C. § 209 and 37 CFR Part 404.

Potential Commercial Applications: Competitive Advantages:
  • A test/screen for infectious prions in live animals and food products
  • Cervid CWD monitoring
  • A human diagnostic for early detection of prion diseases
  • Medical equipment screening
  • A monitor for effectiveness of treatments or disease progression
  • A high through-put screen for inhibitors of prion replication
 
  • Uses a consistent, concentrated source of normal prion protein (rPrP-sen)
  • Prions are detectable to low levels after a single amplification round
  • Demonstrated to be effective at detecting prions from different species
  • May be applicable to blood products, nasal brushings, skin, eye components and other accessible biospecimens
  • Economical and rapid


Inventors:

Ryuichiro Atarashi (NIAID)  ➽ more inventions...

Roger Moore (NIAID)  ➽ more inventions...

Byron Caughey (NIAID)  ➽ more inventions...

Susette Priola (NIAID)  ➽ more inventions...


Intellectual Property:
US Pat: 8,216,788 issued 2012-07-10
US Application No. 14/263,703 filed on 2014-04-28
US Application No. 13/489,321 filed on 2012-06-05
US Application No. 12/177,012 filed on 2008-07-21
PCT Application No. PCT/US2008/070656 filed on 2008-07-21
US Application No. 60/961,364 filed on 2007-07-20

Publications:
Atarashi, Ryuichiro et al. “Simplified ultrasensitive prion detection by recombinant PrP conversion with shaking.” Nature Methods 5, pages 211–212 (2008). PMID 18309304

Collaboration Opportunity:

To license this technology, please contact Jeffrey Thruston at 301-594-5179 or jeffrey.thruston@nih.gov, and reference E-109-2007-0.


Licensing Contact:
Jeffrey Thruston,
Email: jeffrey.thruston@nih.gov
Phone: 301-594-5179

OTT Reference No: E-109-2007-0
Updated: May 29, 2020