Researchers at the University of California San Diego have demonstrated that a key cellular enzyme can accurately read an eight-letter genetic alphabet, doubling the four letters used by all known life on Earth. The finding brings scientists closer to building expanded genetic systems that could perform entirely new biological functions.
Scientists at the University of California San Diego have successfully expanded the genetic alphabet from four letters to eight. This achievement, detailed in research published September 5, 2026, demonstrates that RNA polymerase, an enzyme crucial for reading DNA and producing RNA, can accurately read and transcribe this expanded genetic code. The research suggests existing cellular machinery can handle synthetic genetic information.
The team used biochemical experiments and high-resolution cryo-electron microscopy to observe how RNA polymerase interacts with synthetic DNA letters—artificial genetic letters not found in nature. Detailed imaging revealed that the enzyme recognizes these synthetic letters using similar biochemical and structural signals as it does with natural base pairs. This explains why the enzyme can accurately copy information written using the expanded alphabet.
In a related study published in *PNAS*, the same research team found that RNA polymerase can also recognize another pair of synthetic base pairs even without the hydrogen bonds typically found in DNA. Previous research has already utilized expanded genetic alphabets to create synthetic DNA molecules capable of recognizing liver cancer cells. Researchers believe this new work provides a foundation for technologies built around expanded genetic codes, with potential applications in diagnostics, therapeutics, and engineered biology.
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