Evidence map›Paper›PMID 39271668›Full record

ArticleNature communications2024

Template-dependent DNA ligation for the synthesis of modified oligonucleotides.

Nazarii Sabat, Andreas Stämpfli, Steven Hanlon, Serena Bisagni, Filippo Sladojevich, Kurt Püntener, Marcel Hollenstein

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. RNA therapeutics: current status and future directions.Signal transduction and targeted therapy · 2026
    Review
  2. Article
  3. Review
  4. The XNA alphabet.Nucleic acids research · 2025
    Review
  5. An Update: Enzymatic Synthesis for Industrial Applications.Angewandte Chemie (International ed. in English) · 2025
    Review
  6. 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

7 authors.

Nazarii SabatInstitut Pasteur, Université Paris Cité, CNRS UMR3523, Department of Structural Biology and Chemistry, Laboratory for Bioorganic Chemistry of Nucleic Acids, 28, rue du Docteur Roux, 75724, Paris, Cedex 15, France.ORCID 0000-0001-5400-6000
Andreas StämpfliPharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Basel, Switzerland.
Steven HanlonPharmaceutical Division, Synthetic Molecules Technical Development, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Basel, Switzerland.
Serena BisagniPharmaceutical Division, Synthetic Molecules Technical Development, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Basel, Switzerland.
Filippo SladojevichPharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Basel, Switzerland.
Kurt PüntenerPharmaceutical Division, Synthetic Molecules Technical Development, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Basel, Switzerland.
Marcel HollensteinInstitut Pasteur, Université Paris Cité, CNRS UMR3523, Department of Structural Biology and Chemistry, Laboratory for Bioorganic Chemistry of Nucleic Acids, 28, rue du Docteur Roux, 75724, Paris, Cedex 15, France. marcel.hollenstein2@gmail.com.ORCID 0000-0003-0263-9206

Funding

Agence Nationale de la Recherche (French National Research Agency) ANR-22-PEXM-0002Roche (F. Hoffmann-La Roche Ltd) Technology, Innovation and Science program
6 · The paper itself

Abstract

Chemical modification of DNA is a common strategy to improve the properties of oligonucleotides, particularly for therapeutics and nanotechnology. Existing synthetic methods essentially rely on phosphoramidite chemistry or the polymerization of nucleoside triphosphates but are limited in terms of size, scalability, and sustainability. Herein, we report a robust alternative method for the de novo synthesis of modified oligonucleotides using template-dependent DNA ligation of shortmer fragments. Our approach is based on the fast and scaled accessibility of chemically modified shortmer monophosphates as substrates for the T3 DNA ligase. This method has shown high tolerance to chemical modifications, flexibility, and overall efficiency, thereby granting access to a broad range of modified oligonucleotides of different lengths (20 → 120 nucleotides). We have applied this method to the synthesis of clinically relevant antisense drugs and ultramers containing diverse modifications. Furthermore, the designed chemoenzymatic approach has great potential for diverse applications in therapeutics and biotechnology.

Indexed as

DNADNA LigasesOligonucleotidesOligonucleotides, AntisenseTemplates, GeneticDNADNA LigasesOligonucleotidesOligonucleotides, Antisense

Identifiers

PMID39271668
PMCPMC11399401

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.