ArticleNucleic acids research2013
Development of bis-locked nucleic acid (bisLNA) oligonucleotides for efficient invasion of supercoiled duplex DNA.
Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
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- Anti-gene oligonucleotide clamps invade dsDNA and downregulateMolecular therapy. Nucleic acids · 2024Article
- Artificial genetic polymers against human pathologies.Biology direct · 2022Review
- Oligonucleotides Targeting DNA Repeats DownregulateNucleic acid therapeutics · 2021Article
- Targeted Oligonucleotides for Treating Neurodegenerative Tandem Repeat Diseases.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2019Review
- Oligonucleotide Binding to Non-B-DNA inMolecules (Basel, Switzerland) · 2019Article
- Hydrogel-Assisted Antisense LNA Gapmer Delivery for In Situ Gene Silencing in Spinal Cord Injury.Molecular therapy. Nucleic acids · 2018Article
- LNA effects on DNA binding and conformation: from single strand to duplex and triplex structures.Scientific reports · 2017Article
- CTG repeat-targeting oligonucleotides for down-regulating Huntingtin expression.Nucleic acids research · 2017Article
- Next-generation bis-locked nucleic acids with stacking linker and 2'-glycylamino-LNA show enhanced DNA invasion into supercoiled duplexes.Nucleic acids research · 2016Article
- Disruption of Higher Order DNA Structures in Friedreich's Ataxia (GAA)n Repeats by PNA or LNA Targeting.PloS one · 2016Article
- Synthesis and characterization of oligodeoxyribonucleotides modified with 2'-thio-2'-deoxy-2'-S-(pyren-1-yl)methyluridine.Bioorganic & medicinal chemistry letters · 2015Article
- Oligonucleotide Therapies: The Past and the Present.Human gene therapy · 2015Review
- Triple helical DNA in a duplex context and base pair opening.Nucleic acids research · 2014Article
- Dynamic estrogen receptor interactomes control estrogen-responsive trefoil Factor (TFF) locus cell-specific activities.Molecular and cellular biology · 2014Article
- Recognition of mixed-sequence DNA duplexes: design guidelines for invaders based on 2'-O-(pyren-1-yl)methyl-RNA monomers.The Journal of organic chemistry · 2013Article
- Identification and characterization of second-generation invader locked nucleic acids (LNAs) for mixed-sequence recognition of double-stranded DNA.The Journal of organic chemistry · 2013Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In spite of the many developments in synthetic oligonucleotide (ON) chemistry and design, invasion into double-stranded DNA (DSI) under physiological salt and pH conditions remains a challenge. In this work, we provide a new ON tool based on locked nucleic acids (LNAs), designed for strand invasion into duplex DNA (DSI). We thus report on the development of a clamp type of LNA ON-bisLNA-with capacity to bind and invade into supercoiled double-stranded DNA. The bisLNA links a triplex-forming, Hoogsteen-binding, targeting arm with a strand-invading Watson-Crick binding arm. Optimization was carried out by varying the number and location of LNA nucleotides and the length of the triplex-forming versus strand-invading arms. Single-strand regions in target duplex DNA were mapped using chemical probing. By combining design and increase in LNA content, it was possible to achieve a 100-fold increase in potency with 30% DSI at 450 nM using a bisLNA to plasmid ratio of only 21:1. Although this first conceptual report does not address the utility of bisLNA for the targeting of DNA in a chromosomal context, it shows bisLNA as a promising candidate for interfering also with cellular genes.
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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.