ArticleNucleic acids research2015
Guanabenz (Wytensin™) selectively enhances uptake and efficacy of hydrophobically modified siRNAs.
Article in Nucleic acids research, 2015. 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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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
26 citing papers in PubMed, 42 citations in OpenAlex.
- Staufen dsRNA-binding domain as modules to design bifunctional antibodies for siRNA delivery.Nucleic acids research · 2026Article
- Subcellular Drug Distribution: Exploring Organelle-Specific Characteristics for Enhanced Therapeutic Efficacy.Pharmaceutics · 2024Review
- Between hope and reality: treatment of genetic diseases through nucleic acid-based drugs.Communications biology · 2024Review
- Chloroquine and cytosolic galectins affect endosomal escape of antisense oligonucleotides after Stabilin-mediated endocytosis.Molecular therapy. Nucleic acids · 2023Article
- Therapeutic Oligonucleotides: An Outlook on Chemical Strategies to Improve Endosomal Trafficking.Cells · 2023Review
- Simultaneous inhibition of endocytic recycling and lysosomal fusion sensitizes cells and tissues to oligonucleotide therapeutics.Nucleic acids research · 2023Article
- Delivery of RNA Therapeutics: The Great Endosomal Escape!Nucleic acid therapeutics · 2022Review
- Therapeutic RNA interference: A novel approach to the treatment of primary hyperoxaluria.British journal of clinical pharmacology · 2022Review
- Chemical Manipulation of the Endosome Trafficking Machinery: Implications for Oligonucleotide Delivery.Biomedicines · 2021Review
- Viral Mimicry as a Design Template for Nucleic Acid Nanocarriers.Frontiers in chemistry · 2021Review
- Brief update on endocytosis of nanomedicines.Advanced drug delivery reviews · 2019Review
- Exploiting Nanomaterial-mediated Autophagy for Cancer Therapy.Small methods · 2019Article
- Retro-1-Oligonucleotide Conjugates. Synthesis and Biological Evaluation.Molecules (Basel, Switzerland) · 2019Article
- Messenger RNA Delivery for Tissue Engineering and Regenerative Medicine Applications.Tissue engineering. Part A · 2019Review
- RNAi modulation of placental sFLT1 for the treatment of preeclampsia.Nature biotechnology · 2018Article
- Efficient Gene Silencing in Brain Tumors with Hydrophobically Modified siRNAs.Molecular cancer therapeutics · 2018Article
- Current Challenges in Delivery and Cytosolic Translocation of Therapeutic RNAs.Nucleic acid therapeutics · 2018Review
- Intracellular Trafficking and Endosomal Release of Oligonucleotides: What We Know and What We Don't.Nucleic acid therapeutics · 2018Review
- Comparison of partially and fully chemically-modified siRNA in conjugate-mediated delivery in vivo.Nucleic acids research · 2018Article
- Structure-activity relationships and cellular mechanism of action of small molecules that enhance the delivery of oligonucleotides.Nucleic acids research · 2018Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
One of the major obstacles to the pharmaceutical success of oligonucleotide therapeutics (ONTs) is efficient delivery from the point of injection to the intracellular setting where functional gene silencing occurs. In particular, a significant fraction of internalized ONTs are nonproductively sequestered in endo-lysosomal compartments. Here, we describe a two-step, robust assay for high-throughput de novo detection of small bioactive molecules that enhance cellular uptake, endosomal escape, and efficacy of ONTs. Using this assay, we screened the LOPAC (Sigma-Aldrich) Library of Pharmacologically Active Compounds and discovered that Guanabenz acetate (Wytensin™), an FDA-approved drug formerly used as an antihypertensive agent, is capable of markedly increasing the cellular internalization and target mRNA silencing of hydrophobically modified siRNAs (hsiRNAs), yielding a ∼100-fold decrease in hsiRNA IC50 (from 132 nM to 2.4 nM). This is one of the first descriptions of a high-throughput small-molecule screen to identify novel chemistries that specifically enhance siRNA intracellular efficacy, and can be applied toward expansion of the chemical diversity of ONTs.
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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.