Anastasia Khvorova

This paper introduces fully modified RNA nanostructures (FMRNs) for multi-gene silencing beyond the liver, showing enhanced pharmacokinetics, extrahepatic delivery, and programmable control over siRNA stoichiometry.

This study develops D-siRNA, an albumin-binding dendrimer-conjugated siRNA, showing effective and durable gene silencing in the CNS with no detectable toxicity.

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.

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

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.

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 quantifies huntingtin mRNA expression and aggregation in mouse brains using a high-throughput RNAscope pipeline, revealing heterogeneity in mRNA accumulation and localization across brain regions.

This study delivers IRS2-targeting siRNAs to mammary tumors via albumin-binding dendrimers, reducing tumor growth by inhibiting Irs2 expression and altering tumor microenvironment features.

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

This study investigates how different HTT-lowering therapies affect somatic instability in HD mice, finding that transcriptional repression and CAG repeat binding reduce SI without lowering HTT levels.

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 lowering HTT1a transcript levels delays molecular and neuropathological phenotypes in a Huntington's disease mouse model.

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 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 targeting both DGAT2 in hepatocytes and FASN in stellate cells reduces NASH in mice more effectively than targeting either gene alone.

Silencing MSH3 in the CNS of two models of Huntington's disease using di-valent siRNA blocks disease-accelerating somatic expansion of CAG repeats.

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 study demonstrates the use of protecting oligos to enhance crRNA stability and potency for in vivo genome editing via AAV co-delivery in mice.

The paper develops a machine learning framework for predicting siRNA efficacy using a small dataset by applying trichotomous partitioning and random forest models, achieving better performance than linear models.

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

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