ArticleProceedings of the National Academy of Sciences of the United States of America2017
A semisynthetic organism engineered for the stable expansion of the genetic alphabet.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 201 citations in OpenAlex.
- Substrate Specificity of B12-Depedent Ribonucleotide Reductases: Biotechnology and Metabolic Implications.Chembiochem : a European journal of chemical biology · 2026Article
- High-resolution melting analysis for rapid and cost-effective detection of unnatural base pairs.Biodesign research · 2026Article
- Controlled Delivery and Light-Induced Release of Magic Spot Nucleotides in Escherichia coli.Angewandte Chemie (International ed. in English) · 2026Article
- Omega Nucleic Acids (ΩNA), Ultimate Nucleic Acids for Future Technology.Molecules (Basel, Switzerland) · 2026Review
- Structure-informed models for ionic current prediction in nanopore sequencing of expanded dna alphabets.Nucleic acids research · 2025Article
- Genetic Entanglement Enables Ultrastable Biocontainment in the Mammalian Gut.ACS synthetic biology · 2025Article
- Residue-Specific Incorporation of Noncanonical Amino Acids in Auxotrophic Hosts:Chemical reviews · 2025Review
- Towards next-generation DNA encryption via an expanded genetic system.National science review · 2025Article
- Nucleic acid joining enzymes: biological functions and synthetic applications beyond DNA.The Biochemical journal · 2025Review
- Cracking the Code: Reprogramming the Genetic Script in Prokaryotes and Eukaryotes to Harness the Power of Noncanonical Amino Acids.Chemical reviews · 2024Review
- Engineering tRNAs for the Ribosomal Translation of Non-proteinogenic Monomers.Chemical reviews · 2024Review
- Conformational Morphing by a DNA Analogue Featuring 7-Deazapurines and 5-Halogenpyrimidines and the Origins of Adenine-Tract Geometry.Biochemistry · 2023Article
- Locating, tracing and sequencing multiple expanded genetic letters in complex DNA context via a bridge-base approach.Nucleic acids research · 2023Article
- The Expanded Central Dogma: Genome Resynthesis, Orthogonal Biosystems, Synthetic Genetics.Annual review of biophysics · 2023Review
- Discovery, implications and initial use of semi-synthetic organisms with an expanded genetic alphabet/code.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Interactions of small molecules with DNA junctions.Nucleic acids research · 2022Review
- In vitro evolution of ribonucleases from expanded genetic alphabets.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- From polymerase engineering to semi-synthetic life: artificial expansion of the central dogma.RSC chemical biology · 2022Review
- Rebooting life: engineering non-natural nucleic acids, proteins and metabolites in microorganisms.Microbial cell factories · 2022Review
- Improving the Efficiency and Orthogonality of Genetic Code Expansion.Biodesign research · 2022Review
5 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
All natural organisms store genetic information in a four-letter, two-base-pair genetic alphabet. The expansion of the genetic alphabet with two synthetic unnatural nucleotides that selectively pair to form an unnatural base pair (UBP) would increase the information storage potential of DNA, and semisynthetic organisms (SSOs) that stably harbor this expanded alphabet would thereby have the potential to store and retrieve increased information. Toward this goal, we previously reported that Escherichia coli grown in the presence of the unnatural nucleoside triphosphates dNaMTP and d5SICSTP, and provided with the means to import them via expression of a plasmid-borne nucleoside triphosphate transporter, replicates DNA containing a single dNaM-d5SICS UBP. Although this represented an important proof-of-concept, the nascent SSO grew poorly and, more problematically, required growth under controlled conditions and even then was unable to indefinitely store the unnatural information, which is clearly a prerequisite for true semisynthetic life. Here, to fortify and vivify the nascent SSO, we engineered the transporter, used a more chemically optimized UBP, and harnessed the power of the bacterial immune response by using Cas9 to eliminate DNA that had lost the UBP. The optimized SSO grows robustly, constitutively imports the unnatural triphosphates, and is able to indefinitely retain multiple UBPs in virtually any sequence context. This SSO is thus a form of life that can stably store genetic information using a six-letter, three-base-pair 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.