A team at the University of California San Diego has shown that one of the cell’s most essential enzymes accurately reads an artificially expanded DNA built from eight letters instead of four. The work appeared on 2 September 2026 in Nature Communications.
RNA polymerase recognizes synthetic bases like natural ones
The genetic code of all known life uses four letters: A, T, G and C. So-called hachimoji DNA (Japanese for “eight letters”) adds four synthetic bases that form two extra pairs. The group led by Professor Dong Wang of the Skaggs School of Pharmacy and Pharmaceutical Sciences tested whether RNA polymerase from the bacterium Escherichia coli could process this expanded code. That enzyme reads DNA and rewrites it into RNA, the first step of every gene expression.
Using high-resolution cryo-electron microscopy, the researchers visualized how the enzyme grips the synthetic letters atom by atom. The finding: the polymerase recognizes the synthetic bases through the same chemical and structural signals as the natural ones and transcribes them precisely. This provides the first structural evidence that cells can process synthetic genetic information with their own machinery.
The team sees applications in custom-built biological systems and in new diagnostics and therapeutics. For now it remains foundational lab research; practical use of expanded genetics is a long way off. A companion study from the same group on hydrophobic base pairs appeared in PNAS in August 2026.
Sources: UC San Diego · Nature Communications
