ArticleNature communications2022
Chemical engineering of therapeutic siRNAs for allele-specific gene silencing in Huntington's disease models.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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Who cites it
26 citing papers in PubMed, 46 citations in OpenAlex.
- Treatment of Huntington's disease with a pan-HTT-targeting CRISPR nuclease.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Precision RNAi for Fibrodysplasia Ossificans Progressiva: a combinatorial, unimolecular, allele selective approach.Research square · 2026Article
- RNA-Micelles as Self-Assembling Structures for Efficient Co-Delivery of Synergistic siRNA and Nucleoside Analogues to Treat CRC Lung Metastasis.Advanced functional materials · 2026Article
- Allele-specific knockdown by an engineered DNAzyme capable of RNase H1 evasion.Nucleic acids research · 2026Article
- The Expanding Role of Non-Coding RNAs in Neurodegenerative Diseases: From Biomarkers to Therapeutic Targets.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Nucleic acid therapeutics in neurodegenerative disorders: emerging technologies and clinical landscape.Molecular neurodegeneration advances · 2026Review
- Genetic therapies for neurological diseases.Pharmacological reviews · 2026Review
- Treatment of Huntington's disease with a pan-HTT-targeting CRISPR nuclease.bioRxiv : the preprint server for biology · 2025Article
- Direct RNA sequencing enables improved transcriptome assessment and tracking of RNA modifications for medical applications.Nucleic acids research · 2025Article
- RNA chemistry and therapeutics.Nature reviews. Drug discovery · 2025Review
- A first-in-class EGFR-directed KRAS G12V selective inhibitor.Cancer cell · 2025Article
- Enhancing siRNA efficacy in vivo with extended nucleic acid backbones.Nature biotechnology · 2025Article
- Leveraging plant-derived nanovesicles for advanced nucleic acid-based gene therapy.Theranostics · 2025Review
- Preventing acute neurotoxicity of CNS therapeutic oligonucleotides with the addition of CaMolecular therapy. Nucleic acids · 2024Article
- Evaluation of an Antisense Oligonucleotide Targeting CAG Repeats: A Patient-Customized Therapy Study for Huntington's Disease.Life (Basel, Switzerland) · 2024Article
- Near Sequence Homology Does Not Guarantee siRNA Cross-Species Efficacy.Nucleic acid therapeutics · 2024Article
- Strategies to improve the design of gapmer antisense oligonucleotide on allele-specific silencing.Molecular therapy. Nucleic acids · 2024Article
- Identification of selective and non-selectiveMolecular therapy. Nucleic acids · 2024Article
- A programmable dual-targeting siRNA scaffold supports potent two-gene modulation in the central nervous system.Nucleic acids research · 2024Article
- Preventing acute neurotoxicity of CNS therapeutic oligonucleotides with the addition of CabioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
Small interfering RNAs are a new class of drugs, exhibiting sequence-driven, potent, and sustained silencing of gene expression in vivo. We recently demonstrated that siRNA chemical architectures can be optimized to provide efficient delivery to the CNS, enabling development of CNS-targeted therapeutics. Many genetically-defined neurodegenerative disorders are dominant, favoring selective silencing of the mutant allele. In some cases, successfully targeting the mutant allele requires targeting single nucleotide polymorphism (SNP) heterozygosities. Here, we use Huntington's disease (HD) as a model. The optimized compound exhibits selective silencing of mutant huntingtin protein in patient-derived cells and throughout the HD mouse brain, demonstrating SNP-based allele-specific RNAi silencing of gene expression in vivo in the CNS. Targeting a disease-causing allele using RNAi-based therapies could be helpful in a range of dominant CNS disorders where maintaining wild-type expression is essential.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.