ReviewNucleic acids research2025
From liquid-phase synthesis to chemical ligation: preparation of oligonucleotides and their backbone analogs in solution.
Review in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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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.
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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.
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Who cites it
2 citing papers in PubMed.
- Emerging strategies and innovations in circular RNA synthesis.Molecular therapy. Nucleic acids · 2026Review
- Translational opportunities in aptamer and nanobody lateral flow assays within the WHO REASSURED framework.Sensors & diagnostics · 2026Review
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Authors and funding
1 author.
Funding
Abstract
The increasing need for sustainably produced oligonucleotides and their chemically modified counterparts has inspired numerous alternative scalable and greener production methods. Current manufacturing techniques depend on automated solid-phase synthesis and polymerase-based assembly, but liquid-phase synthesis and alternative engineered biocatalytic methods are emerging to meet the scale-up challenges. The scale, length, and modifications of the target nucleic acid product dictate the choice of protocol, which can be a combination of chemical and/or biocatalytic methods. While modern biocatalytic methods are competitive for the preparation of long oligonucleotides (up to 1 kb), liquid-phase synthesis is gaining a strong foothold for the large-scale preparation of short sequences (<30-mers), especially for the chemically modified therapeutic oligonucleotides. DNA-templated chemical ligation is an emerging technology expected to expand the range of liquid-phase synthesis to the production of longer sequences. This review focuses on oligonucleotide synthesis carried out exclusively in solution. Current protocols for liquid-phase synthesis of oligonucleotides and their backbone analogs, and template-assisted chemical ligation, yielding the phosphodiester linkage and its artificial mimics of biological relevance, are summarized.
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Registered trials
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