Cyclic amplification of prion protein misfolding: rationale, applications, and perspectives

Prion replication is a slow process in vivo. We have recently described a procedure to induce accelerated prion replication in vitro based on the cyclic amplification of prion protein misfolding (PMCA) [Saborio et al., 2001]. This procedure, conceptually analogous to DNA amplification by PCR, has tremendous implications for research and diagnosis [Soto, 2002; Soto et al., 2002]. This chapter describes the principles behind this novel technology, the current status of development, and its applications for understanding the molecular basis of the prion infectious agent (PrPSc) and for developing ultrasensitive diagnostic procedures.