ArticleBioconjugate chemistry2017
Synthesis and Evaluation of Parenchymal Retention and Efficacy of a Metabolically Stable O-Phosphocholine-N-docosahexaenoyl-l-serine siRNA Conjugate in Mouse Brain.
Article in Bioconjugate chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
- Strategies to Improve the Lipophilicity of Hydrophilic Macromolecular Drugs.Advanced healthcare materials · 2026Review
- Phosphatidylcholine-derived carriers facilitate brain tumor delivery and enhance glioblastoma therapy.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
- Enhancing siRNA efficacy in vivo with extended nucleic acid backbones.Nature biotechnology · 2025Article
- CNS Delivery of Nucleic Acid Therapeutics: Beyond the Blood-Brain Barrier and Towards Specific Cellular Targeting.Pharmaceutical research · 2023Review
- Modulating the Blood-Brain Barrier: A Comprehensive Review.Pharmaceutics · 2021Review
- Advances in the Design of (Nano)Formulations for Delivery of Antisense Oligonucleotides and Small Interfering RNA: Focus on the Central Nervous System.Molecular pharmaceutics · 2021Review
- Therapeutic siRNA: state of the art.Signal transduction and targeted therapy · 2020Review
- A divalent siRNA chemical scaffold for potent and sustained modulation of gene expression throughout the central nervous system.Nature biotechnology · 2019Article
- Current Aspects of siRNA Bioconjugate for In Vitro and In Vivo Delivery.Molecules (Basel, Switzerland) · 2019Review
- The valency of fatty acid conjugates impacts siRNA pharmacokinetics, distribution, and efficacy in vivo.Journal of controlled release : official journal of the Controlled Release Society · 2019Article
- Diverse lipid conjugates for functional extra-hepatic siRNA delivery in vivo.Nucleic acids research · 2019Article
- Hydrophobicity drives the systemic distribution of lipid-conjugated siRNAs via lipid transport pathways.Nucleic acids research · 2019Article
- Current Development of siRNA Bioconjugates: From Research to the Clinic.Frontiers in pharmacology · 2019Review
- Gene Silencing in the Right Place at the Right Time.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- Transvascular Delivery of Hydrophobically Modified siRNAs: Gene Silencing in the Rat Brain upon Disruption of the Blood-Brain Barrier.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- Optimized Cholesterol-siRNA Chemistry Improves Productive Loading onto Extracellular Vesicles.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- Enhanced Intercellular Delivery of cRGD-siRNA Conjugates by an Additional Oligospermine Modification.ACS omega · 2018Article
- Hydrophobicity of Lipid-Conjugated siRNAs Predicts Productive Loading to Small Extracellular Vesicles.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- Efficient Gene Silencing in Brain Tumors with Hydrophobically Modified siRNAs.Molecular cancer therapeutics · 2018Article
- Improving siRNA Delivery In Vivo Through Lipid Conjugation.Nucleic acid therapeutics · 2018Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Ligand-conjugated siRNAs have the potential to achieve targeted delivery and efficient silencing in neurons following local administration in the central nervous system (CNS). We recently described the activity and safety profile of a docosahexaenoic acid (DHA)-conjugated, hydrophobic siRNA (DHA-hsiRNA) targeting Huntingtin (Htt) mRNA in mouse brain. Here, we report the synthesis of an amide-modified, phosphocholine-containing DHA-hsiRNA conjugate (PC-DHA-hsiRNA), which closely resembles the endogenously esterified biological structure of DHA. We hypothesized that this modification may enhance neuronal delivery in vivo. We demonstrate that PC-DHA-hsiRNA silences Htt in mouse primary cortical neurons and astrocytes. After intrastriatal delivery, Htt-targeting PC-DHA-hsiRNA induces ∼80% mRNA silencing and 71% protein silencing after 1 week. However, PC-DHA-hsiRNA did not substantially outperform DHA-hsiRNA under the conditions tested. Moreover, at the highest locally administered dose (4 nmol, 50 μg), we observe evidence of PC-DHA-hsiRNA-mediated reactive astrogliosis. Lipophilic ligand conjugation enables siRNA delivery to neural tissues, but rational design of functional, nontoxic siRNA conjugates for CNS delivery remains challenging.
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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.