ArticleMolecular therapy : the journal of the American Society of Gene Therapy2011
Rational design of therapeutic siRNAs: minimizing off-targeting potential to improve the safety of RNAi therapy for Huntington's disease.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 81 citations in OpenAlex.
- From rules to foundation models: a comprehensive review of machine learning approaches for siRNA design.NAR genomics and bioinformatics · 2026Review
- Bridging development and disease: the potential of LncRNAs as biomarkers and therapeutics in pediatric neurological disorders.Pediatric research · 2026Review
- miRNA gene mutations commonly disrupt the proper functioning of miRNA genes.Science advances · 2026Article
- Preclinical Development of a Vectorized Artificial miRNA Gene Therapy for Tauopathies.bioRxiv : the preprint server for biology · 2025Article
- Current trends in gene therapy to treat inherited disorders of the brain.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
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- Delivering therapeutic RNA into the brain using extracellular vesicles.Molecular therapy. Nucleic acids · 2024Review
- AAV-based in vivo gene therapy for neurological disorders.Nature reviews. Drug discovery · 2023Review
- Mutation-agnostic RNA interference with engineered replacement rescuesLife science alliance · 2023Article
- Delivering the Promise of Gene Therapy with Nanomedicines in Treating Central Nervous System Diseases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Review
- Limited astrocyte-to-neuron conversion in the mouse brain using NeuroD1 overexpression.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Human miRNA miR-675 inhibits DUX4 expression and may be exploited as a potential treatment for Facioscapulohumeral muscular dystrophy.Nature communications · 2021Article
- miR‑101a‑3p overexpression prevents acetylcholine‑CaClMolecular medicine reports · 2021Article
- Effects of mutant huntingtin inactivation on Huntington disease-related behaviours in the BACHD mouse model.Neuropathology and applied neurobiology · 2021Article
- PIAS1 modulates striatal transcription, DNA damage repair, and SUMOylation with relevance to Huntington's disease.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Effective and Accurate Gene Silencing by a Recombinant AAV-Compatible MicroRNA Scaffold.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- AAV5-miHTT Gene Therapy Demonstrates Broad Distribution and Strong Human Mutant Huntingtin Lowering in a Huntington's Disease Minipig Model.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- Systemic Delivery of MicroRNA Using Recombinant Adeno-associated Virus Serotype 9 to Treat Neuromuscular Diseases in Rodents.Journal of visualized experiments : JoVE · 2018Article
- Pre-clinical Safety and Off-Target Studies to Support Translation of AAV-Mediated RNAi Therapy for FSHD.Molecular therapy. Methods & clinical development · 2018Article
- Gene suppression approaches to neurodegeneration.Alzheimer's research & therapy · 2017Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
RNA interference (RNAi) provides an approach for the treatment of many human diseases. However, the safety of RNAi-based therapies can be hampered by the ability of small inhibitory RNAs (siRNAs) to bind to unintended mRNAs and reduce their expression, an effect known as off-target gene silencing. Off-targeting primarily occurs when the seed region (nucleotides 2-8 of the small RNA) pairs with sequences in 3'-UTRs of unintended mRNAs and directs translational repression and destabilization of those transcripts. To date, most therapeutic RNAi sequences are selected primarily for gene silencing efficacy, and later evaluated for safety. Here, in designing siRNAs to treat Huntington's disease (HD), a dominant neurodegenerative disorder, we prioritized selection of sequences with minimal off-targeting potentials (i.e., those with a scarcity of seed complements within all known human 3'-UTRs). We identified new promising therapeutic candidate sequences which show potent silencing in cell culture and mouse brain. Furthermore, we present microarray data demonstrating that off-targeting is significantly minimized by using siRNAs that contain "safe" seeds, an important strategy to consider during preclinical development of RNAi-based therapeutics.
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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.