ArticleACS applied materials & interfaces2020
Self-Assembled DNA-PEG Bottlebrushes Enhance Antisense Activity and Pharmacokinetics of Oligonucleotides.
Article in ACS applied materials & interfaces, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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Who cites it
11 citing papers in PubMed.
- Hydrolytically Degradable Polyethylene Glycol Bottlebrush Polymers Address the Stability-Clearance Trade-Off for Drug Delivery.Polymer science & technology (Washington, D.C.) · 2026Article
- Bottlebrush polymer conjugates for enhanced antisense oligonucleotide therapy in myotonic dystrophy type 1.Nucleic acids research · 2026Article
- Generation of topologically defined linear and cyclic DNA bottle brush polymersPolymer chemistry · 2025Article
- Targeting the Skin: The Study of a Bottlebrush Polymer-Antisense Oligonucleotide Conjugate in a Psoriasis Mouse Model.Small (Weinheim an der Bergstrasse, Germany) · 2024Article
- Inhalable Bottlebrush Polymer Bioconjugates as Vectors for Efficient Pulmonary Delivery of Oligonucleotides.ACS nano · 2024Article
- Complex DNA Architectonics─Self-Assembly of Amphiphilic Oligonucleotides into Ribbons, Vesicles, and Asterosomes.Bioconjugate chemistry · 2023Article
- Rational Design of Porous Poly(ethylene glycol) Films as a Matrix for ssDNA Immobilization and Hybridization.Bioengineering (Basel, Switzerland) · 2022Article
- Targeting oncogenic KRAS with molecular brush-conjugated antisense oligonucleotides.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Composites of Nucleic Acids and Boron Clusters (CInternational journal of molecular sciences · 2021Article
- Synthetic Approaches for Copolymers Containing Nucleic Acids and Analogues: Challenges and Opportunities.Polymer chemistry · 2021Article
- RNA-based therapies: A cog in the wheel of lung cancer defense.Molecular cancer · 2021Review
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
Herein, we report a novel strategy to enhance the antisense activity and the pharmacokinetics of therapeutic oligonucleotides. Through the DNA hybridization chain reaction, DNA hairpins modified with poly(ethylene glycol) (PEG) form a bottlebrush architecture consisting of a double-stranded DNA backbone, PEG side chains, and antisense overhangs. The assembled structure exhibits high PEG density on the surface, which suppresses unwanted interactions between the DNA and proteins (e.g., enzymatic degradation) while allowing the antisense overhangs to hybridize with the mRNA target and thereby deplete target protein expression. We show that these PEGylated bottlebrushes targeting oncogenic KRAS can achieve much higher antisense efficacy compared with unassembled hairpins with or without PEGylation and can inhibit the proliferation of lung cancer cells bearing the G12C mutant KRAS gene. Meanwhile, these structures exhibit elevated blood retention times in vivo due to the biological stealth properties of PEG and the high molecular weight of the overall assembly. Collectively, this self-assembly approach bears the characteristics of a simple, safe, yet highly translatable strategy to improve the biopharmaceutical properties of therapeutic oligonucleotides.
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