ArticleNucleic acids research2019
A novel and translational role for autophagy in antisense oligonucleotide trafficking and activity.
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 12 papers.
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Who cites it
12 citing papers in PubMed.
- Naked antisense oligonucleotides remain endolysosomally sequestered despite induced membrane damage.bioRxiv : the preprint server for biology · 2026Article
- Ultrasmall nanoparticles for co-delivery of antisense oligonucleotides targeting miR-21 and miR-210 to treat glioblastoma.Journal of nanobiotechnology · 2025Article
- Endosomal Escape and Nuclear Localization: Critical Barriers for Therapeutic Nucleic Acids.Molecules (Basel, Switzerland) · 2024Review
- The Coming Age of Antisense Oligos for the Treatment of Hepatic Ischemia/Reperfusion (IRI) and Other Liver Disorders: Role of Oxidative Stress and Potential Antioxidant Effect.Antioxidants (Basel, Switzerland) · 2024Review
- Simultaneous inhibition of endocytic recycling and lysosomal fusion sensitizes cells and tissues to oligonucleotide therapeutics.Nucleic acids research · 2023Article
- Antisense Oligonucleotide-Mediated Silencing of Mitochondrial Fusion and Fission Factors Modulates Mitochondrial Dynamics and Rescues Mitochondrial Dysfunction.Nucleic acid therapeutics · 2022Article
- Combined effects of a ketogenic diet and exercise training alter mitochondrial and peroxisomal substrate oxidative capacity in skeletal muscle.American journal of physiology. Endocrinology and metabolism · 2021Article
- Chemical Manipulation of the Endosome Trafficking Machinery: Implications for Oligonucleotide Delivery.Biomedicines · 2021Review
- Functional Nucleic-Acid-Decorated Spherical Nanoparticles: Preparation Strategies and Current Applications in Cancer Therapy.Small science · 2021Article
- Differential Response of Hippocampal and Cerebrocortical Autophagy and Ketone Body Metabolism to the Ketogenic Diet.Frontiers in cellular neuroscience · 2021Article
- Article
- Increased PIP3 activity blocks nanoparticle mRNA delivery.Science advances · 2020Article
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endocytosis is a mechanism by which cells sense their environment and internalize various nutrients, growth factors and signaling molecules. This process initiates at the plasma membrane, converges with autophagy, and terminates at the lysosome. It is well-established that cellular uptake of antisense oligonucleotides (ASOs) proceeds through the endocytic pathway; however, only a small fraction escapes endosomal trafficking while the majority are rendered inactive in the lysosome. Since these pathways converge and share common molecular machinery, it is unclear if autophagy-related trafficking participates in ASO uptake or whether modulation of autophagy affects ASO activity and localization. To address these questions, we investigated the effects of autophagy modulation on ASO activity in cells and mice. We found that enhancing autophagy through small-molecule mTOR inhibition, serum-starvation/fasting, and ketogenic diet, increased ASO-mediated target reduction in vitro and in vivo. Additionally, autophagy activation enhanced the localization of ASOs into autophagosomes without altering intracellular concentrations or trafficking to other compartments. These results support a novel role for autophagy and the autophagosome as a previously unidentified compartment that participates in and contributes to enhanced ASO activity. Further, we demonstrate non-chemical methods to enhance autophagy and subsequent ASO activity using translatable approaches such as fasting or ketogenic diet.
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