(256b) Engineering Anti-Prion Scfv for the Treatment of Prion Diseases

Prion diseases are a group of rapidly progressing, lethal neurodegenerative diseases for which there currently is no treatment available. Prions are propagated by the conversion of the native form of the prion protein (PrP^C) to an alternatively folded, disease causing form (PrP^Sc) catalyzed by the interaction of PrP^Sc with PrP^C. Previous researchers have developed antibodies that bind PrP^C and slow the conversion to PrP^Sc in cell culture and animal models, though few attempts have been made to engineer existing antibodies for greater therapeutic effect. We are engineering anti-PrP^C single chain antibody fragments (α-PrP^C scFvs) with improved affinity, stability, and pH sensitivity through sorting of a yeast surface display library by fluorescence activated cell sorting (FACS). Measurements obtained from isolated clones provide inputs for a quantitative mathematical model, which will guide future improvements. The model and methods developed here will likely apply more generally to passive immunity and cell based therapies for other neurological diseases.