Rachael Miller

Divalent siRNA for prion disease

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.

Blocking somatic repeat expansion and lowering huntingtin via RNA interference synergize to prevent Huntingtons disease pathogenesis in mice

This study shows that combining RNAi to silence MSH3 and HTT reduces huntingtin inclusions and restores gene expression in HD mice.

Intrastriatal delivery of a zinc finger protein targeting the mutant HTT gene by AAV9 obviates lipid phenotypes in brain and plasma of zQ175DN HD mice

The paper shows that reducing mutant HTT with a zinc finger protein in HD mice prevents lipid changes in brain and plasma.

Mutant Huntingtin exon1 protein detected in mouse brain with neoepitope antibody: effects of CAG repeat expansion, MSH3 silencing, and aggregation

The paper detects HTT1a protein in Huntington's disease mouse brain using western blot with neo-epitope antibodies and shows that reducing MSH3 lowers HTT1a levels.

Preventing acute neurotoxicity of CNS therapeutic oligonucleotides with the addition of Ca2+ and Mg2+ in the formulation

This study shows adding high concentrations of Ca2+ and Mg2+ to oligonucleotide formulations prevents acute neurotoxicity in CNS delivery without affecting efficacy.

mRNA nuclear clustering leads to a difference in mutant huntingtin mRNA and protein silencing by siRNAs in vivo

The paper shows that di-valent siRNA reduces wild-type Htt mRNA but not mutant HTT mRNA in HD mouse models, with mutant transcripts remaining clustered in the nucleus.

Chemical engineering of therapeutic siRNAs for allele-specific gene silencing in vivo in CNS

This paper demonstrates allele-specific siRNA silencing of mutant huntingtin in CNS using SNP-based targeting in vitro and in vivo.