Juliana E Gentile

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

Divalent siRNA 2439-s4 lowers human PrP to 17% residual in transgenic mouse brain after one dose, and a separate mouse Prnp-targeting siRNA extends survival in prion-infected mice.

This paper introduces pan-ExM-t, an all-optical method for visualizing specific proteins in the ultrastructural context of brain tissue, demonstrating its application on various markers in mouse brain sections and neuron cultures.

The paper assesses the cell-type-specific activity of intrathecally delivered antisense oligonucleotides in deep brain regions of non-human primates, finding broad target engagement across neuronal and non-neuronal cells.

This study identifies a cryptic exon in the human PRNP gene that can reduce prion protein expression when included in mRNA, offering a new therapeutic target for prion disease.

The paper maps antisense oligonucleotide activity in the brain using single-cell transcriptomics in mice and macaques, showing widespread target suppression across cell types with varying durations.