RNA polymerase reads eight-letter DNA alphabet in UC San Diego studies
New CapabilitiesE. coli enzyme transcribes four synthetic Hachimoji letters alongside DNA's natural four
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Overview
Updated 2 hours agoAll life on Earth runs on four DNA letters. Researchers at UC San Diego have shown that one of biology's core enzymes can read an eight-letter alphabet that includes four synthetic letters. The finding, published in Nature Communications, is a step toward engineered biological systems that use genetic information nature never wrote.
The work tests whether a cell's own machinery can process synthetic DNA. RNA polymerase from E. coli recognized the artificial letters through the same structural signals it uses for natural ones. That opens the door to expanded genetic systems for diagnostics, therapeutics, and data storage.
Why it matters
If expanded genetic alphabets work inside cells, scientists could build biological systems that produce compounds and functions not found in nature.
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People Involved
Organizations Involved
The pharmacy school at UC San Diego where Dong Wang's lab conducted the research.
Research foundation in Alachua, Florida, where Steven Benner designed the Hachimoji alphabet.
Timeline
February 2019 September 2026
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ScienceDaily reports the finding
Latest MediaThe university's research alert is republished, drawing wider attention to the eight-letter alphabet.
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Hachimoji transcription study published
PublicationNature Communications paper showed E. coli RNA polymerase transcribes all eight letters at near-natural rates.
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Hydrophobic base pair study published
PublicationPNAS paper showed RNA polymerase recognizes a synthetic pair without hydrogen bonds.
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RNA polymerase recognizes artificial base pairs
PublicationUC San Diego showed RNA polymerase can't distinguish synthetic AEGIS base pairs from natural ones.
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Hachimoji alphabet introduced
PublicationBenner and colleagues published the eight-letter genetic alphabet in Science, adding four synthetic nucleotides.
Historical Context
3 moments from history that rhyme with this story — and how they unfolded.
Romesberg's semi-synthetic organism (2014)
Floyd Romesberg's lab at Scripps Research created a semi-synthetic organism with an unnatural base pair (d5SICS-dNaM) in its DNA. The bacterium E. coli replicated the synthetic pair alongside its natural DNA.
The semi-synthetic organism showed that cells can replicate DNA with unnatural letters.
It demonstrated the feasibility of expanded genetic systems in living cells, though the pair was later refined.
Romesberg's work showed replication of unnatural letters in cells; the new study addresses transcription, the next step in gene expression.
Hachimoji alphabet introduction (2019)
Steven Benner and colleagues published the Hachimoji eight-letter genetic alphabet in Science. The alphabet added four synthetic nucleotides to DNA's natural four, and an engineered T7 RNA polymerase could transcribe it.
The alphabet was demonstrated in vitro with a simple viral enzyme.
It set the stage for testing whether cellular enzymes could handle the expanded alphabet.
The 2026 study answers the question the 2019 paper left open: whether a cell's own multi-subunit RNA polymerase can read all eight letters.
AEGIS six-letter system (2000s–2020s)
Benner's earlier AEGIS (Artificially Expanded Genetic Information System) added two letters to DNA's four. Six-letter AEGIS DNA aptamers carrying P and Z have been engineered to target liver cancer cells and carry chemotherapy drugs.
AEGIS demonstrated practical applications of expanded alphabets in diagnostics and therapeutics.
It provided the foundation for the eight-letter Hachimoji system.
The new work extends AEGIS's P:Z pair to the full eight-letter alphabet and shows cellular RNA polymerase can read it.
