ArticleNucleic acid therapeutics2017
Pharmacokinetic Profiling of Conjugated Therapeutic Oligonucleotides: A High-Throughput Method Based Upon Serial Blood Microsampling Coupled to Peptide Nucleic Acid Hybridization Assay.
Article in Nucleic acid therapeutics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed.
- Albumin-binding dendrimer-conjugated siRNA enables safe and effective gene silencing throughout the central nervous system.Nucleic acids research · 2026Article
- An siRNA targetingMolecular therapy. Nucleic acids · 2026Article
- Divalent siRNA for prion disease.Nucleic acids research · 2026Article
- Divalent siRNA for prion disease.bioRxiv : the preprint server for biology · 2026Article
- Intradermal delivery of lipophilic siRNAs enables prolonged skin retention and sustained gene silencing in a porcine model.Nature communications · 2026Article
- RNA-Micelles as Self-Assembling Structures for Efficient Co-Delivery of Synergistic siRNA and Nucleoside Analogues to Treat CRC Lung Metastasis.Advanced functional materials · 2026Article
- Potent and durable gene modulation in heart and muscle with chemically defined lipophilic siRNAs.Nucleic acids research · 2025Article
- Intravenous lipid-siRNA conjugate mediates gene silencing at the blood-brain barrier and blood-CSF barrier.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
- Albumin-binding dendritic siRNA improves delivery and efficacy to solid tumors in a melanoma model.Molecular therapy. Nucleic acids · 2025Article
- siRNA conjugate with high albumin affinity and degradation resistance for delivery and treatment of arthritis in mice and guinea pigs.Nature biomedical engineering · 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
- Metabolic Stability and Targeted Delivery of Oligonucleotides: Advancing RNA Therapeutics Beyond The Liver.Journal of medicinal chemistry · 2025Review
- Microsampling in toxicology studies - maximising the scientific, business and 3Rs advantages.Toxicology research · 2025Article
- Lipid-siRNA conjugate accesses perivascular transport and achieves durable knockdown throughout the central nervous system.bioRxiv : the preprint server for biology · 2024Article
- RNAi-based drug design: considerations and future directions.Nature reviews. Drug discovery · 2024Review
- Single intravitreal administration of a tetravalent siRNA exhibits robust and efficient gene silencing in mouse and pig photoreceptors.Molecular therapy. Nucleic acids · 2024Article
- Structural optimization of siRNA conjugates for albumin binding achieves effective MCL1-directed cancer therapy.Nature communications · 2024Article
- Cholesterol Conjugates of Small Interfering RNA: Linkers and Patterns of Modification.Molecules (Basel, Switzerland) · 2024Article
- Dendritic amphiphilic siRNA: Selective albumin binding,Molecular therapy. Nucleic acids · 2023Article
- Challenges of Assessing Exon 53 Skipping of the HumanNucleic acid therapeutics · 2023Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Therapeutic oligonucleotides, such as small interfering RNAs (siRNAs), hold great promise for the treatment of incurable genetically defined disorders by targeting cognate toxic gene products for degradation. To achieve meaningful tissue distribution and efficacy in vivo, siRNAs must be conjugated or formulated. Clear understanding of the pharmacokinetic (PK)/pharmacodynamic behavior of these compounds is necessary to optimize and characterize the performance of therapeutic oligonucleotides in vivo. In this study, we describe a simple and reproducible methodology for the evaluation of in vivo blood/plasma PK profiles and tissue distribution of oligonucleotides. The method is based on serial blood microsampling from the saphenous vein, coupled to peptide nucleic acid hybridization assay for quantification of guide strands. Performed with minimal number of animals, this method allowed unequivocal detection and sensitive quantification without the need for amplification, or further modification of the oligonucleotides. Using this methodology, we compared plasma clearances and tissue distribution profiles of two different hydrophobically modified siRNAs (hsiRNAs). Notably, cholesterol-hsiRNA presented slow plasma clearances and mainly accumulated in the liver, whereas, phosphocholine-docosahexaenoic acid-hsiRNA was rapidly cleared from the plasma and preferably accumulated in the kidney. These data suggest that the PK/biodistribution profiles of modified hsiRNAs are determined by the chemical nature of the conjugate. Importantly, the method described in this study constitutes a simple platform to conduct pilot assessments of the basic clearance and tissue distribution profiles, which can be broadly applied for evaluation of new chemical variants of siRNAs and micro-RNAs.
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