Generation of prions in vitro and the protein-only hypothesis

Prions are self-propagating proteinaceous infectious agents capable of transmitting disease in the absence of nucleic acids. The nature of the infectious agent in prion diseases has been at the center of passionate debate for the past 30 years. However, recent reports on the in vitro generation of prions have settled all doubts that the misfolded prion protein (PrP(Sc)) is the key component in propagating infectivity. However, we still do not understand completely the mechanism of prion replication and whether or not other cellular factors besides PrP(Sc) are required for infectivity. In this article, we discuss these recent reports under the context of the protein-only hypothesis and their implications.