ArticleNature2014
A semi-synthetic organism with an expanded genetic alphabet.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 206 papers.
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Who cites it
206 citing papers in PubMed.
- Quantifying replication fidelity of unnatural base pairs using nanopore sequencing.Nature communications · 2026Article
- The Emergence of Life in the Light of Evolution.ArXiv · 2026Article
- Single-residue engineering of Klenow fragment enables broad acceptance of chemically modified nucleotides.Nucleic acids research · 2026Article
- High-resolution melting analysis for rapid and cost-effective detection of unnatural base pairs.Biodesign research · 2026Article
- MDNA : a software module for DNA structure generation and analysis.Nucleic acids research · 2026Article
- High-Affinity Six-Letter DNA XenoAptamer Generation by Genetic Alphabet Expansion.Journal of the American Chemical Society · 2026Article
- Beyond the Sequence: Chemical and Topological Design and Innovations in mRNA Therapeutics.Chemical reviews · 2026Review
- Controlled Delivery and Light-Induced Release of Magic Spot Nucleotides in Escherichia coli.Angewandte Chemie (International ed. in English) · 2026Article
- Stability and Reactivity of Alternative Nucleobases in Concentrated Sulfuric Acid.Molecules (Basel, Switzerland) · 2026Article
- Omega Nucleic Acids (ΩNA), Ultimate Nucleic Acids for Future Technology.Molecules (Basel, Switzerland) · 2026Review
- Expanding DNA alphabet adds a previously unknown dimension to nanostructures.Science advances · 2026Article
- Long Single-Stranded DNA with Site-Specific Modifications to Enable Single-Base-Resolution Epigenetics.Angewandte Chemie (International ed. in English) · 2026Article
- Recognition of unnatural base pairs by a eukaryotic DNA polymerase enables universal sequencing of an expanded genetic alphabet.Nucleic acids research · 2026Article
- From mRNA stabilisation to mirror life: Biological orthogonality, incremental risk, and anticipatory governance.Frontiers in bioengineering and biotechnology · 2026Article
- Expanded genetic alphabet increases structural and chemical diversity of six-letter DNA for high-affinity protein-targeting aptamers.Nature communications · 2025Article
- Engineering and Assay of Enzymes for Expanded Genetic Alphabet Replication.Biochemistry · 2025Article
- An unnatural base pair for the detection of epigenetic cytosine modifications in DNA.Nature chemistry · 2025Article
- Sequencing a DNA analog composed of artificial bases.Nature communications · 2025Article
- Direct high-throughput deconvolution of non-canonical bases via nanopore sequencing and bootstrapped learning.Nature communications · 2025Article
- Article
146 more citing papers are in PubMed but not listed here.
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8 authors.
Funding
Abstract
Organisms are defined by the information encoded in their genomes, and since the origin of life this information has been encoded using a two-base-pair genetic alphabet (A-T and G-C). In vitro, the alphabet has been expanded to include several unnatural base pairs (UBPs). We have developed a class of UBPs formed between nucleotides bearing hydrophobic nucleobases, exemplified by the pair formed between d5SICS and dNaM (d5SICS-dNaM), which is efficiently PCR-amplified and transcribed in vitro, and whose unique mechanism of replication has been characterized. However, expansion of an organism's genetic alphabet presents new and unprecedented challenges: the unnatural nucleoside triphosphates must be available inside the cell; endogenous polymerases must be able to use the unnatural triphosphates to faithfully replicate DNA containing the UBP within the complex cellular milieu; and finally, the UBP must be stable in the presence of pathways that maintain the integrity of DNA. Here we show that an exogenously expressed algal nucleotide triphosphate transporter efficiently imports the triphosphates of both d5SICS and dNaM (d5SICSTP and dNaMTP) into Escherichia coli, and that the endogenous replication machinery uses them to accurately replicate a plasmid containing d5SICS-dNaM. Neither the presence of the unnatural triphosphates nor the replication of the UBP introduces a notable growth burden. Lastly, we find that the UBP is not efficiently excised by DNA repair pathways. Thus, the resulting bacterium is the first organism to propagate stably an expanded genetic alphabet.
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Registered trials
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.