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Non-natural nucleobase systems for expanded information storage, PCR and diagnostics, aptamer evolution, site-specific labeling, protein engineering, and synthetic biology beyond A, T(U), G and C.
Artificial base pair systems introduce non-natural nucleobases that recognize complementary partners while remaining embedded in a DNA- or RNA-like scaffold. Unlike backbone or sugar modifications, these systems change the information-bearing bases and create additional pairing relationships beyond A:T(U) and G:C.
Bio-Synthesis supports project review for Benner AEGIS dP:dZ and dB:dS, dIsoC:dIsoG, Hirao dDs:dPx, Romesberg dNaM:dTPT3, Hachimoji systems and selected emerging bases.
Adds orthogonal genetic letters.
Hydrogen-bonded or hydrophobic pairing.
Selected systems support replication or transcription.
Enables aptamers, labeling and protein engineering.
Nomenclature: dP, dZ, dB, dS, dIsoC, dIsoG, dDs, dPx, dNaM and dTPT3.
Notes: Check marks indicate feasible placement formats for project review, not blanket stock availability. RNA compatibility may require enzymatic workflows or dedicated ribonucleoside chemistry. Additional research bases such as dPn, dPa, d5SICS, dMMO2, s, y, ImN, NaO and CTPT3 can be evaluated when a structure or publication is provided.
Select your project goal to see the recommended artificial base-pair family, why it fits, common alternatives, practical applications and the main technical consideration.
dP:dZ is the strongest general starting point for expanding genetic information while preserving a Watson–Crick-like hydrogen-bonding framework. It is central to AEGIS and also contributes to larger expanded-alphabet systems.
Replication fidelity and sequence-context performance must be validated in the complete enzyme system.
These hydrogen-bonded systems are strong starting points for orthogonal amplification, internal controls and diagnostic workflows. dP:dZ offers broader expanded-alphabet potential, while dIsoC:dIsoG is especially useful for control sequences and detection systems.
PCR
Diagnostics
Orthogonality
“PCR compatible” is polymerase-, sequence- and cycle-dependent.
dDs:dPx is the strongest starting point for expanded-alphabet aptamer discovery because the hydrophobic base pair adds chemical diversity and has a strong history in ExSELEX and high-affinity aptamer generation.
Aptamers
Chemical Diversity
Selection value depends on reliable amplification and retention of the artificial pair.
dNaM:dTPT3 has the strongest history in expanded codons, semi-synthetic organisms and noncanonical amino acid incorporation. It is the preferred starting point when the goal extends from DNA storage into transcription and translation.
Protein Engineering
In Vivo Use
System Complexity
The entire replication, transcription and translation system must be engineered together.
Hirao-family systems are well suited to site-specific labeling because functionalized artificial-base substrates can be incorporated at defined positions through engineered replication or transcription workflows.
Labeling
RNA Production
Functional Diversity
Chemical incorporation and enzyme-mediated labeling require different substrates and workflows.
dNaM:dTPT3 is the most established system for maintaining an unnatural base pair in living cells and retrieving expanded information through transcription and translation.
In Vivo Retention
Translation
Complexity
Triphosphate transport, replication fidelity and cellular fitness all influence success.
dP and dZ form an orthogonal hydrogen-bonded pair with Watson–Crick-like geometry.
Individual Bases
Pairing
Best Known For
View dP:dZ Guide →
dB and dS form a second AEGIS pair used in orthogonal primer and assembly workflows.
View dB:dS Guide →
A historically important hydrogen-bonded expanded pair used in diagnostics and PCR research.
Bases
View IsoC:IsoG Guide →
A hydrophobic pair associated with semi-synthetic organisms and expanded translation.
View NaM:TPT3 Guide →
A Hirao hydrophobic pair used in PCR, ExSELEX, high-affinity aptamers and labeling.
View Ds:Px Guide →
Eight genetic letters forming four orthogonal pairs for predictable expanded information systems.
Alphabet
Pairs
View Hachimoji Guide →
Recognition based on shape, packing and exclusion of water.
Selected artificial pairs can be retained under optimized amplification conditions.
Artificial pairs create orthogonal controls, primers and probes with reduced natural-genome cross-talk.
New C-nucleosides, hydrolysis-stable partners and expanded aromatic systems continue to emerge.
A successful artificial-base project usually combines chemical synthesis with assay-specific enzymology and analytical confirmation.
The workflow can be adapted for direct chemical incorporation, enzyme-mediated labeling, aptamer selection, diagnostics or expanded-translation studies.
Choose dP:dZ, dB:dS, IsoC:IsoG, Ds:Px, NaM:TPT3 or another system based on the intended application.
Define sequence, artificial-base position, scale, purification, terminal labels and analytical requirements.
Use a compatible polymerase or transcription system and verify retention of the artificial base pair.
Use the product in diagnostics, aptamer selection, labeling, protein engineering or expanded-genetic studies.
Relative ratings summarize the maturity and typical usefulness of each family for common applications. Actual performance remains polymerase-, sequence- and workflow-dependent.
Ratings are directional, not absolute specifications. Polymerase choice, sequence context, cycle count, substrate form and assay design can materially change performance.
Artificial base pairs expand the chemical and informational capabilities of nucleic acids across diagnostics, molecular evolution, synthetic biology and protein engineering.
Add orthogonal genetic letters and pairing relationships beyond natural DNA.
Create orthogonal controls, primers and detection systems with reduced natural cross-talk.
Expand library chemistry with hydrophobic and orthogonal nucleobases.
Create expanded codons for noncanonical amino acid incorporation.
Direct functional-group incorporation into DNA or RNA at defined positions.
Retain, transcribe and retrieve expanded genetic information in living cells.
Labeled probes and transcripts.
Modular ligands and surfaces.
Capture and enrichment.
PS, LNA/BNA or other compatible modifications.
LNA/BNA, ENA, cEt, AmNA and NMA.
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UNA and related analogs.
GNA, TNA, HNA, CeNA, FANA, tcDNA, aTNA and SNA.
Chiral PS, PACE, PNA and Morpholino.
Monomer availability, incorporation chemistry, purification, MS compatibility and duplex requirements.
Controlled production, project-specific purification, analytical QC, documentation and packaging.
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