University of California San Diego researchers expand genetic alphabet

Researchers at the University of California San Diego have demonstrated that RNA polymerase, the enzyme responsible for transcribing DNA into RNA, can accurately read and process an expanded eight-letter genetic alphabet. While all known life relies on a four-letter DNA code, this breakthrough shows that biological machinery can be utilized to handle synthetic genetic information.

Using high-resolution cryo-electron microscopy, the team observed RNA polymerase from Escherichia coli recognizing and incorporating synthetic base pairs. The study revealed that the enzyme utilizes the same biochemical and structural signals for these artificial letters as it does for natural ones. Additionally, related research indicated that the enzyme can recognize synthetic base pairs even in the absence of hydrogen bonds.

Separately, advancements in synthetic biology have led to the creation of bottom-up protein assemblies designed to act as efficient RNA transport systems. Using artificial intelligence to design protein architectures, researchers developed over 100 synthetic vehicles with unique symmetries. These vehicles have demonstrated high RNA transfer efficiency and programmable targeting capabilities in cellular models and animal studies.