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.

PLoS Pathogens · May 26, 2026Peer-reviewedNeuroscience

Divalent siRNA for prion disease

Juliana E Gentile, Taylor L Corridon, Fiona E. Serack, Dimas Echeverria, Zachary Kennedy, Corrie L. Gallant‐Behm, Matthew R. Hassler, Garth A. Kinberger, Margaret N Kelemen, Nikita G Kamath, Yuan Lian, Katherine Y. Gross, Rachael Miller, Kendrick DeSouza-Lenz, Michael Howard, , Sonia M. Vallabh

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.

Nucleic Acids Research · Mar 19, 2026Peer-reviewedNeuroscience✦ In-depth digest

Cell type distribution of intrathecal antisense oligonucleotide activity in deep brain regions of non-human primates

Jeannine A. Frei, Juliana E Gentile, Yuan Lian, Meredith A Mortberg, Juliana S. Capitanio, Paymaan Jafar‐Nejad, Sonia M. Vallabh, Hien Tran Zhao, Eric Vallabh Minikel

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.

Nucleic Acid Therapeutics · Sep 6, 2025Peer-reviewedNeuroscience

Zinc Finger Repressors mediate widespread PRNP lowering in the nonhuman primate brain and profoundly extend survival in prion disease mice

Shih-Wei Chou, Meredith A Mortberg, Kimberly Marlen, David S. Ojala, Toufan Parman, Michael Howard, Kendrick DeSouza-Lenz, Yuan Lian, Mohadeseh Mehrabian, Matthew R. Tiffany, Annemarie Ledeboer, Patrick Dunn, Jing Hu, Kenia Guzman, Nikita Kamath, , Bryan Zeitler

This study demonstrates that Zinc Finger Repressors (ZFRs) reduce prion protein (PrP) expression in nonhuman primates and extend survival in prion disease mice.

bioRxiv · Mar 5, 2025 · PreprintNeuroscience