ArticleNature biotechnology2025
Template-independent enzymatic synthesis of RNA oligonucleotides.
Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Primer- and template-independent RNA polymerization by terminal nucleotidyltransferase TENT4B.Nucleic acids research · 2026Article
- RNA-based therapeutics for Alzheimer's disease and related tauopathies: challenges and opportunities.The journal of prevention of Alzheimer's disease · 2026Review
- A Universal Nucleoside-to-Nucleoside-5'-Triphosphate Enzyme Cascade Driven by Polyphosphate.Angewandte Chemie (International ed. in English) · 2026Article
- Review
- Beyond the Sequence: Chemical and Topological Design and Innovations in mRNA Therapeutics.Chemical reviews · 2026Review
- Computational evolution of poly(U) polymerase for efficient and controlled RNA oligonucleotide synthesis.Nucleic acids research · 2026Article
- Aspergillus fumigatus PolX1 is an early ancestor of vertebrate terminal deoxynucleotidyl transferases.Nucleic acids research · 2026Article
- Enzymatic synthesis of key RNA therapeutic building blocks using simple phosphate donors.Nature communications · 2025Article
- RNA chemistry and therapeutics.Nature reviews. Drug discovery · 2025Review
- Pore-Based RNA Evaluation for Control of Integrity, Sequence, and Errors - Quality Control (PRECISE-QC).bioRxiv : the preprint server for biology · 2025Article
- An Update: Enzymatic Synthesis for Industrial Applications.Angewandte Chemie (International ed. in English) · 2025Review
- Article
- Template-independent enzymatic synthesis of RNA oligonucleotides.Nature biotechnology · 2025Article
- Development, opportunities, and challenges of siRNA nucleic acid drugs.Molecular therapy. Nucleic acids · 2025Review
- Engineering Considerations for Developing Next-Generation Oligonucleotide Therapeutics.Nature chemical engineering · 2024Article
- Functional characterization of LSM12 as a driver in uveal melanoma oncogenesis.Advances in ophthalmology practice and researchArticle
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RNA oligonucleotides have emerged as a powerful therapeutic modality to treat disease, yet current manufacturing methods may not be able to deliver on anticipated future demand. Here, we report the development and optimization of an aqueous-based, template-independent enzymatic RNA oligonucleotide synthesis platform as an alternative to traditional chemical methods. The enzymatic synthesis of RNA oligonucleotides is made possible by controlled incorporation of reversible terminator nucleotides with a common 3'-O-allyl ether blocking group using new CID1 poly(U) polymerase mutant variants. We achieved an average coupling efficiency of 95% and demonstrated ten full cycles of liquid phase synthesis to produce natural and therapeutically relevant modified sequences. We then qualitatively assessed the platform on a solid phase, performing enzymatic synthesis of several N + 5 oligonucleotides on a controlled-pore glass support. Adoption of an aqueous-based process will offer key advantages including the reduction of solvent use and sustainable therapeutic oligonucleotide manufacturing.
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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.