Samuel R. Hildebrand

Single-dose administration of therapeutic divalent siRNA targeting MECP2 prevents lethality for one year in an MECP2 duplication mouse model

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

Mismatch repair dissection by in vivo RNAi reveals dose-dependent modulators of somatic instability and proteome remodeling in Huntingtons disease

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

C57BL/6 BAC-CAG Huntingtons disease mice show somatic CAG expansion and responses to small interfering RNAs comparable to the FVB strain

The paper compares somatic CAG expansion and siRNA responses in C57BL/6 and FVB BAC-CAG HD mouse models, finding comparable expansion and MSH3-targeted siRNA efficacy.

Organyl 5'-Phosphates in siRNA Guide Strands: Structure-Function Relationships Governing Anchoring in Argonaute 2 and Metabolic Stability

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

Potent and durable gene modulation in heart and muscle with chemically defined siRNAs

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

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.

A programmable dual-targeting di-valent siRNA scaffold supports potent multi-gene modulation in the central nervous system

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.

Formamide significantly enhances the efficiency of chemical adenylation of RNA sequencing ligation adaptors

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

Silencing of ApoE with Divalent siRNAs Drives Activation of Immune Clearance Pathways and Improves Amyloid Pathology in Mouse Models of Alzheimer's Disease

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