Evidence map›Paper›PMID 28887512›Full record

ArticleScientific reports2017

LNA effects on DNA binding and conformation: from single strand to duplex and triplex structures.

Y Vladimir Pabon-Martinez, You Xu, Alessandra Villa, Karin E Lundin, Sylvain Geny, Chi-Hung Nguyen, Erik B Pedersen, Per T Jørgensen, Jesper Wengel, Lennart Nilsson and 2 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
2.2field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Editorial:Molecular therapy. Nucleic acids · 2022
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Targeted Oligonucleotides for Treating Neurodegenerative Tandem Repeat Diseases.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2019
    Review
  16. Article
  17. Article
  18. Article
  19. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 3 countries.

Y Vladimir Pabon-MartinezDepartment of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, SE-141 86, Huddinge, Stockholm, Sweden.ORCID 0000-0002-4732-2635
You XuDepartment of Biosciences and Nutrition, Karolinska Institutet, SE-141 83, Huddinge, Sweden.
Alessandra VillaDepartment of Biosciences and Nutrition, Karolinska Institutet, SE-141 83, Huddinge, Sweden.ORCID 0000-0002-9573-0326
Karin E LundinDepartment of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, SE-141 86, Huddinge, Stockholm, Sweden.
Sylvain GenyDepartment of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, SE-141 86, Huddinge, Stockholm, Sweden.
Chi-Hung NguyenInstitut Curie, PSL Research University, UMR 9187-U 1196, CNRS-Institut Curie, INSERM, Centre Universitaire, Orsay, France.
Erik B PedersenDepartment of Physics, Chemistry and Pharmacy, Nucleic Acid Center, University of Southern Denmark, DK-5230, Odense M, Denmark.
Per T JørgensenDepartment of Physics, Chemistry and Pharmacy, Nucleic Acid Center, University of Southern Denmark, DK-5230, Odense M, Denmark.ORCID 0000-0003-3932-5921
Jesper WengelDepartment of Physics, Chemistry and Pharmacy, Nucleic Acid Center, University of Southern Denmark, DK-5230, Odense M, Denmark.
Lennart NilssonDepartment of Biosciences and Nutrition, Karolinska Institutet, SE-141 83, Huddinge, Sweden.ORCID 0000-0002-5067-6397
C I Edvard SmithDepartment of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, SE-141 86, Huddinge, Stockholm, Sweden.ORCID 0000-0003-1907-3392
Rula ZainDepartment of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, SE-141 86, Huddinge, Stockholm, Sweden. rula.zain@ki.se.ORCID 0000-0001-8327-846X
Karolinska Institutet · SEUniversity of Southern Denmark · DKCentre National de la Recherche Scientifique · FRKarolinska University Hospital · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The anti-gene strategy is based on sequence-specific recognition of double-strand DNA by triplex forming (TFOs) or DNA strand invading oligonucleotides to modulate gene expression. To be efficient, the oligonucleotides (ONs) should target DNA selectively, with high affinity. Here we combined hybridization analysis and electrophoretic mobility shift assay with molecular dynamics (MD) simulations to better understand the underlying structural features of modified ONs in stabilizing duplex- and triplex structures. Particularly, we investigated the role played by the position and number of locked nucleic acid (LNA) substitutions in the ON when targeting a c-MYC or FXN (Frataxin) sequence. We found that LNA-containing single strand TFOs are conformationally pre-organized for major groove binding. Reduced content of LNA at consecutive positions at the 3'-end of a TFO destabilizes the triplex structure, whereas the presence of Twisted Intercalating Nucleic Acid (TINA) at the 3'-end of the TFO increases the rate and extent of triplex formation. A triplex-specific intercalating benzoquinoquinoxaline (BQQ) compound highly stabilizes LNA-containing triplex structures. Moreover, LNA-substitution in the duplex pyrimidine strand alters the double helix structure, affecting x-displacement, slide and twist favoring triplex formation through enhanced TFO major groove accommodation. Collectively, these findings should facilitate the design of potent anti-gene ONs.

Indexed as

DNAElectrophoretic Mobility Shift AssayFrataxinGenes, mycIron-Binding ProteinsMolecular Dynamics SimulationNucleic Acid ConformationNucleic Acid HybridizationOligonucleotidesDNAFrataxinIron-Binding ProteinsOligonucleotides

Identifiers

PMID28887512
PMCPMC5591256
OpenAlexW2751193807

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.