Dimas Echeverria

One Scaffold, Many Targets: Fully Modified RNA Nanostructures for Multi-Gene Silencing Beyond the Liver

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.

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.

Fully Modified SpyCas9 Guide RNAs Enable Robust Genome Editing In Cells and In Vivo

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

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.

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.

Therapeutic delivery of albumin-binding siRNA targeting IRS2 to diverse cell types reduces mammary tumor growth

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.

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.

Cryopreservation of siRNA-treated cells is feasible

This study shows that cryopreservation of siRNA-treated cells maintains silencing efficacy, with optimal siRNA exposure duration and temperature.

Structure - silencing duration relationships in RNAi medicines in rapidly dividing cells

This study examines how chemical modifications affect the duration of RNAi-based therapies in rapidly dividing cells, finding that specific modifications can extend silencing duration significantly.

Lowering the HTT1a transcript as an effective therapy for Huntingtons disease

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

RNAi-mediated silencing of SOD1 profoundly extends survival and functional outcomes in ALS mice

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

miRNA Mimic Optimization: Chemical Structure - Activity - Targetome Relationship to Engineer Selective Anti-Tumor Immunity in T cells

This study identifies a miR-374b mimic that selectively inhibits GVHD while enhancing GvL, demonstrating the potential of chemically modified miRNA therapies to improve T-cell-based cancer treatments.

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.

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.

Single intravitreal administration of a tetravalent siRNA exhibits robust and efficient gene silencing in rodent and swine photoreceptors

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.

Lactate transporter MCT1 in hepatic stellate cells promotes fibrotic collagen expression in nonalcoholic steatohepatitis

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

Dual targeting of hepatocyte DGAT2 and stellate cell FASN alleviates nonalcoholic steatohepatitis in mice.

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.

Self-delivering CRISPR RNAs for AAV Co-delivery and Genome Editing in vivo

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.

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.

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.