ArticleNucleic acids research2019
Quantitative fluorescence imaging determines the absolute number of locked nucleic acid oligonucleotides needed for suppression of target gene expression.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- Safety and toxicity assessment of antisense oligonucleotides in brain-relevant human cellular models.Molecular therapy. Nucleic acids · 2026Review
- Time- and spatially resolved LNA delivery via thermally controlled SPION technology.Molecular therapy. Nucleic acids · 2026Article
- Naked antisense oligonucleotides remain endolysosomally sequestered despite induced membrane damage.bioRxiv : the preprint server for biology · 2026Article
- Generalizable, high-throughput image analysis of subcellular structures using dispersion indices.iScience · 2026Article
- Heteroduplex oligonucleotide technology boosts gene knockdown in cardiac and skeletal muscles.Nucleic acids research · 2026Article
- Impact of uniform illumination in widefield microscopy and mesoscopy.Scientific reports · 2025Article
- A CRISPR/Cas9 screen reveals proteins at the endosome-Golgi interface that modulate cellular anti-sense oligonucleotide activity.Nature communications · 2025Article
- Elucidating brain transport pathways and cell type-dependent gene silencing of a durable lipid-siRNA conjugate administered into cerebrospinal fluid.Nucleic acids research · 2025Article
- Multimodal imaging of a liver-on-a-chip model using labelled and label-free optical microscopy techniques.Lab on a chip · 2024Article
- Peptide Conjugates of a 2'-ACS omega · 2023Article
- GOLGA8 increases bulk antisense oligonucleotide uptake and activity in mammalian cells.Molecular therapy. Nucleic acids · 2023Article
- Endosomal escape of RNA therapeutics: How do we solve this rate-limiting problem?RNA (New York, N.Y.) · 2023Article
- Single-cell quantification and dose-response of cytosolic siRNA delivery.Nature communications · 2023Article
- Chemistry of Therapeutic Oligonucleotides That Drives Interactions with Biomolecules.Pharmaceutics · 2022Review
- Delivery of RNA Therapeutics: The Great Endosomal Escape!Nucleic acid therapeutics · 2022Review
- The non-coding RNA (ncRNA)-mediated high expression of polycomb group factor 1 (PCGF1) is a prognostic biomarker and is correlated with tumor immunity infiltration in liver hepatocellular carcinoma.Annals of translational medicine · 2022Article
- Self-assembled tetrahedral framework nucleic acid mediates tumor-associated macrophage reprogramming and restores antitumor immunity.Molecular therapy. Nucleic acids · 2022Article
- Quantitative Measurement of Cytosolic and Nuclear Penetration of Oligonucleotide Therapeutics.ACS chemical biology · 2022Article
- Innovative developments and emerging technologies in RNA therapeutics.RNA biology · 2022Article
- Assessing the Cellular Uptake, Endosomal Escape, and Cytosolic Entry Efficiencies of Cyclic Peptides.Methods in molecular biology (Clifton, N.J.) · 2022Article
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Locked nucleic acid based antisense oligonucleotides (LNA-ASOs) can reach their intracellular RNA targets without delivery modules. Functional cellular uptake involves vesicular accumulation followed by translocation to the cytosol and nucleus. However, it is yet unknown how many LNA-ASO molecules need to be delivered to achieve target knock down. Here we show by quantitative fluorescence imaging combined with LNA-ASO microinjection into the cytosol or unassisted uptake that ∼105 molecules produce >50% knock down of their targets, indicating that a substantial amount of LNA-ASO escapes from endosomes. Microinjected LNA-ASOs redistributed within minutes from the cytosol to the nucleus and remained bound to nuclear components. Together with the fact that RNA levels for a given target are several orders of magnitude lower than the amounts of LNA-ASO, our data indicate that only a minor fraction is available for RNase H1 mediated reduction of target RNA. When non-specific binding sites were blocked by co-administration of non-related LNA-ASOs, the amount of target LNA-ASO required was reduced by an order of magnitude. Therefore, dynamic processes within the nucleus appear to influence the distribution and activity of LNA-ASOs and may represent important parameters for improving their efficacy and potency.
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