Ken Yamada

The paper develops fully modified SpyCas9 guide RNAs that maintain or enhance genome editing efficacy in vitro and in vivo.

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 study identifies organyl 5'-phosphate mimics that enhance AGO2 binding and metabolic stability by interacting with a hydrophobic pocket in the MID domain.

This study develops chemically defined siRNAs for durable gene modulation in muscle and heart, showing long-term silencing and functional benefits with minimal toxicity.

The paper shows that silencing SOD1 with optimized di-siRNA extends survival and prevents disease progression in ALS mice.

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.

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

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.

This paper introduces a dual-targeting di-valent siRNA scaffold that can silence two genes simultaneously in the CNS of mice, demonstrating potent and programmable multi-gene modulation.

This paper introduces a chemical adenylation method using formamide that achieves >90% yield for RNA sequencing ligation adaptors, improving scalability and reducing cleanup steps.

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