Nicholas McHugh

Therapeutic siRNAs provide safe and durable modulation of MECP2 for the treatment of mild and severe MECP2 Duplication Syndrome.

The paper uses RNAi to identify dose-dependent MMR gene modulators of somatic instability and proteome changes in HD mouse models.

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

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

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 study evaluates tetravalent siRNA configurations for photoreceptor gene silencing, finding that tetravalent siRNA provides robust, long-lasting efficacy with a good safety profile in rodent and swine models.

This study shows that MCT1 in hepatic stellate cells promotes collagen expression in NASH, while hepatocyte MCT1 does not significantly affect fibrosis.

This study shows that silencing ApoE in the brain with divalent siRNAs reduces amyloid plaques in Alzheimer's mice without affecting systemic cholesterol.