Evidence map›Paper›PMID 25679211›Full record

ArticlePloS one2015

Stereospecificity of oligonucleotide interactions revisited: no evidence for heterochiral hybridization and ribozyme/DNAzyme activity.

Kai Hoehlig, Lucas Bethge, Sven Klussmann

Abstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
–field-weighted citation impact
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

17 citing papers in PubMed.

  1. Spiegelmer Aptamers: Innovative Approach in Breast Cancer.Breast cancer : basic and clinical research · 2026
    Review
  2. Heterochiral modifications enhance robustness and function of DNA in living human cells.Chembiochem : a European journal of chemical biology · 2024
    Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Assembly of long L-RNA by native RNA ligation.Chemical communications (Cambridge, England) · 2021
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. l-DNA-Based Catalytic Hairpin Assembly Circuit.Molecules (Basel, Switzerland) · 2020
    Article
  14. Article
  15. Heterochiral Nucleic Acid Circuits.Emerging topics in life sciences · 2019
    Article
  16. Mirror-Image Oligonucleotides: History and Emerging Applications.Chemistry (Weinheim an der Bergstrasse, Germany) · 2019
    Review
  17. Article
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

3 authors.

Kai HoehligNOXXON Pharma AG, Berlin, Germany.
Lucas BethgeNOXXON Pharma AG, Berlin, Germany.
Sven KlussmannNOXXON Pharma AG, Berlin, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

A major challenge for the application of RNA- or DNA-oligonucleotides in biotechnology and molecular medicine is their susceptibility to abundant nucleases. One intriguing possibility to tackle this problem is the use of mirror-image (l-)oligonucleotides. For aptamers, this concept has successfully been applied to even develop therapeutic agents, so-called Spiegelmers. However, for technologies depending on RNA/RNA or RNA/DNA hybridization, like antisense or RNA interference, it has not been possible to use mirror-image oligonucleotides because Watson-Crick base pairing of complementary strands is (thought to be) stereospecific. Many scientists consider this a general principle if not a dogma. A recent publication proposing heterochiral Watson-Crick base pairing and sequence-specific hydrolysis of natural RNA by mirror-image ribozymes or DNAzymes (and vice versa) prompted us to systematically revisit the stereospecificity of oligonucleotides hybridization and catalytic activity. Using hyperchromicity measurements we demonstrate that hybridization only occurs among homochiral anti-parallel complementary oligonucleotide strands. As expected, achiral PNA hybridizes to RNA and DNA irrespective of their chirality. In functional assays we could not confirm an alleged heterochiral hydrolytic activity of ribozymes or DNAzymes. Our results confirm a strict stereospecificity of oligonucleotide hybridization and clearly argue against the possibility to use mirror-image oligonucleotides for gene silencing or antisense applications.

Indexed as

Base SequenceDNA, CatalyticNucleic Acid HybridizationOligonucleotidesRNA, CatalyticStereoisomerismSubstrate SpecificityDNA, CatalyticOligonucleotidesRNA, Catalytic

Identifiers

PMID25679211
PMCPMC4334536

What OpenQuestion holds

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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.