The in vitro bioassay systems for the amplification and detection of abnormal prion PrP(Sc) in blood and tissues

Abstract

Prion diseases or transmissible spongiform encephalopathies, including Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD), are chronic neurodegenerative diseases characterized by accumulation of abnormal infectious prions known as PrPSc. Infectious prion is emerging as a blood transfusion-transmissible pathogen and is present at extremely low levels in the blood of asymptomatic patients, which is not detectable by current standard methodologies. As such, prion-related diseases impose a huge challenge to blood transfusion services around the world. Rapid, sensitive, and specific assays are thus urgently needed to detect trace amounts of infectious prions in the blood or tissues of asymptomatic patients, as early diagnostic blood transfusion and screening tools. Recent advances in the in vitro assay technologies including protein misfolding cyclic amplification and immunoassays have made it possible to detect infectious prions in the blood of animals with scrapie and even of asymptomatic animals infected with prions. These assays thus bring some hope for the possibility of detecting infectious prions in human blood and tissues for both early diagnosis for blood transfusion and transplantation screening purposes. This review focuses on the development of the various in vitro bioassay systems for the rapid amplification and detection of infectious prions that might be present in blood and tissues for blood transfusion and transplantation recipients.