PRNP and prion disease: In the case of prion diseases, where neurodegeneration is due to replication of the endogenous prion protein in the presence of the infectious agents, the prion, there are efforts at developing silencing agents to lower PRNP expression and reduce cellular prion protein expression, with the hope to attenuate prion-induced neurodegeneration or even prevent it in at risk individuals (e.g. pre-symptomatic carriers of highly penetrant mutations) (Nuvolone et al., 2009).