ArticleNucleic acids research2019
Characterization of the interactions of chemically-modified therapeutic nucleic acids with plasma proteins using a fluorescence polarization assay.
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 81 papers, 1 of them a synthesis that pooled it.
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Who cites it
81 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.
- Dissolving microneedles for nucleic acid delivery: A systematic search, review, and data synthesis.Acta biomaterialia · 2025Pooled it
- RNA therapeutics: current status and future directions.Signal transduction and targeted therapy · 2026Review
- Albumin-binding dendrimer-conjugated siRNA enables safe and effective gene silencing throughout the central nervous system.Nucleic acids research · 2026Article
- Neutral Backbone Modifications Enhance the Pharmacokinetics and Biodistribution of Antibody-Oligonucleotide Conjugates with High Drug-to-Antibody Ratios.Journal of medicinal chemistry · 2026Article
- The Versatile Applications of Antisense Oligonucleotides in Modern Medicine.International journal of molecular sciences · 2026Review
- ClinASO: An open-source platform for rapid drug discovery of gapmer antisense oligonucleotides.Molecular therapy. Nucleic acids · 2026Article
- Cyanine-modified ssODNs enhance CRISPR-Cas9 HDR in stem cell embryo models via chromatin and chemical modulation.Nature communications · 2026Article
- Guanine base modifications in antisense oligonucleotides mitigate acute central nervous system toxicity.RSC chemical biology · 2026Article
- Advances in antisense oligonucleotide treatment for cancer.Japanese journal of clinical oncology · 2026Review
- Acute neuronal inhibition response caused by phosphorothioate antisense oligonucleotides following local delivery to the central nervous system.Nucleic acids research · 2026Article
- Heteroduplex oligonucleotide technology boosts gene knockdown in cardiac and skeletal muscles.Nucleic acids research · 2026Article
- RNA-based therapeutic opportunities for the treatment of kidney diseases.Nature reviews. Nephrology · 2026Review
- DNA/RNA Heteroduplex Oligonucleotide for Highly Efficient Gene Silencing.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Morpholino-RNA duplex exhibits robust, sustained, and safe steric-block antisense activity by intracerebroventricular and intrathecal injection.Nature communications · 2025Article
- Solution-Phase Synthesis of Boranophosphate and Boranophosphate/Phosphorothioate/Phosphate Chimeric Oligonucleotides via the H-Boranophosphonate Method.The Journal of organic chemistry · 2025Article
- Chemical engineering of CRISPR-Cas systems for therapeutic application.Nature reviews. Drug discovery · 2025Review
- Self-Assembly and Biological Properties of Highly Fluorinated Oligonucleotide Amphiphiles.Angewandte Chemie (International ed. in English) · 2025Article
- Photochemical Stabilization of Self-Assembled Spherical Nucleic Acids.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- Evolution of antisense oligonucleotides: navigating nucleic acid chemistry and delivery challenges.Expert opinion on drug discovery · 2025Review
- Development of bioconjugate-based delivery systems for nucleic acids.RNA (New York, N.Y.) · 2024Review
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interactions of chemically modified nucleic acid therapeutics with plasma proteins play an important role in facilitating distribution from the injection site to peripheral tissues by reducing renal clearance. Despite the importance of these interactions, analytical methods that can characterize binding constants with individual plasma proteins in a reliable and high throughput manner are not easily available. We developed a fluorescence polarization (FP) based assay and measured binding constants for the 25 most abundant human plasma proteins with phosphorothioate (PS) modified antisense oligonucleotides (ASOs). We evaluated the influence of sequence, sugar modifications, and PS content on ASO interactions with several abundant human plasma proteins and determined the effect of salt and pH on these interactions. PS ASOs were found to associate predominantly with albumin and histidine-rich glycoprotein (HRG) in mouse and human plasma by size-exclusion chromatography. In contrast, PS ASOs associate predominantly with HRG in monkey plasma because of higher concentrations of this protein in monkeys. Finally, plasma proteins capable of binding PS ASOs in human plasma were confirmed by employing affinity chromatography and proteomics. Our results indicate distinct differences in contributions from the PS backbone, nucleobase composition and oligonucleotide flexibility to protein binding.
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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.