Daniel A. Sprague

This study demonstrates that deep PrP lowering with a potent siRNA prevents prion disease symptoms in mice and extends survival in symptomatic animals.

The paper describes BI-TfR1 CapX, a gene delivery vector that efficiently crosses the blood-brain barrier, transduces CNS neurons and astrocytes, and reduces Prnp mRNA with low doses.

The paper identifies two small molecules that lower PrP levels in cultured cells but show limited activity in human cell lines and in vivo.

The paper introduces hmSEEKR, a k-mer-based hidden Markov model that identifies non-linear sequence similarities in transcriptomes, revealing functional RNA domains with biological relevance.

The paper measures PrP half-life in vivo and shows it limits the time to effect of PrP-lowering therapies, with implications for drug development and clinical trial design.