ArticleMolecular therapy. Nucleic acids2020
Cell Type Impacts Accessibility of mRNA to Silencing by RNA Interference.
Article in Molecular therapy. Nucleic acids, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- A novel bispecific siRNA concept: Efficient dual knockdown ofMolecular therapy. Nucleic acids · 2025Article
- Strict retroelement regulation is frequently lost following cancer transformation and generates a promising reservoir of cancer biomarkers.Mobile DNA · 2025Article
- Systematic analysis of siRNA and mRNA features impacting fully chemically modified siRNA efficacy.Nucleic acids research · 2025Article
- Mechanistic intracellular PK/PD modeling to inform development strategies for small interfering RNA therapeutics.Molecular therapy. Nucleic acids · 2025Article
- Identification of selective and non-selectiveMolecular therapy. Nucleic acids · 2024Article
- mRNA Nuclear Clustering Leads to a Difference in Mutant Huntingtin mRNA and Protein Silencing by siRNAsNucleic acid therapeutics · 2024Article
- A combinatorial approach for achieving CNS-selective RNAi.Nucleic acids research · 2024Article
- RNAi-based drug design: considerations and future directions.Nature reviews. Drug discovery · 2024Review
- mRNA nuclear clustering leads to a difference in mutant huntingtin mRNA and protein silencing by siRNAsbioRxiv : the preprint server for biology · 2024Article
- Silencing Apoe with divalent-siRNAs improves amyloid burden and activates immune response pathways in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Rational design of a JAK1-selective siRNA inhibitor for the modulation of autoimmunity in the skin.Nature communications · 2023Article
- Di-valent siRNA-mediated silencing of MSH3 blocks somatic repeat expansion in mouse models of Huntington's disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Single-cell quantification and dose-response of cytosolic siRNA delivery.Nature communications · 2023Article
- Review
- Structures and Applications of Nucleic Acid-Based Micelles for Cancer Therapy.International journal of molecular sciences · 2023Review
- Unlocking the potential of RNA-based therapeutics in the lung: current status and future directions.Frontiers in genetics · 2023Review
- RNAi-based modulation of IFN-γ signaling in skin.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Drug delivery systems for RNA therapeutics.Nature reviews. Genetics · 2022Review
- Mutant huntingtin messenger RNA forms neuronal nuclear clusters in rodent and human brains.Brain communications · 2022Article
- Insight Into the Prospects for RNAi Therapy of Cancer.Frontiers in pharmacology · 2021Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
RNA interference (RNAi) is a potent mechanism that silences mRNA and protein expression in all cells and tissue types. RNAi is known to exert many of its functional effects in the cytoplasm, and thus, the cellular localization of target mRNA may impact observed potency. Here, we demonstrate that cell identity has a profound impact on accessibility of apolipoprotein E (ApoE) mRNA to RNAi. We show that, whereas both neuronal and glial cell lines express detectable ApoE mRNA, in neuronal cells, ApoE mRNA is not targetable by RNAi. Screening of a panel of thirty-five chemically modified small interfering RNAs (siRNAs) did not produce a single hit in a neuronal cell line, whereas up to fifteen compounds showed strong efficacy in glial cells. Further investigation of the cellular localization of ApoE mRNA demonstrates that ApoE mRNA is partially spliced and preferentially localized to the nucleus (∼80%) in neuronal cells, whereas more than 90% of ApoE mRNA is cytoplasmic in glial cells. Such an inconsistency in intracellular localization and splicing might provide an explanation for functional differences in RNAi compounds. Thus, cellular origin might have an impact on accessibility of mRNA to RNAi and should be taken into account during the screening process.
Identifiers
What OpenQuestion holds
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.