PMCA. A Decade of In Vitro Prion Replication

Natalia      Fernandez-Borges; Joaquin      Castilla

Abstract

Protein Misfolding Cyclic Amplification (PMCA) is a 10 years old in vitro technique based on a cyclic process leading to accelerate prion replication in vitro. The technique has been modified and adapted several times since its inception: new ideas, more sophisticated equipments and new applications have been essential elements for its upgrading. PMCA has proved to be an efficient method mimicking in vitro some of the fundamental steps involved in prion replication in vivo. Thus, it can be used to efficiently replicate a variety of infectious prion strains/species maintaining their strain specificity. It is an eminent technique for TSE diagnosis and is being used for detecting prions in blood in presymptomatic samples. On the other hand, the in vitro prion replication has been decisive to prove the protein only hypothesis, thanks to the generation of infectious prions by using substrates based exclusively on recombinant PrPC without any mammalian or synthetic co-factors. These achievements, in addition to the ability of PMCA for generating de novo prions in vitro as well as its use for evaluating the potential risks of different prion strains to humans and animals, make this technique as one of the most important tools from the last decade in the prion field.

Keywords: In vitro replication, PMCA, prion, scrapie, Transmissible Spongiform Encephalopathy (TSE)

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