A recent paper in Nature, from the Church Lab at Harvard Medical School & the Wyss Institute introduces AGENTEX (automated genetic tRNA expansion), a robotic, multiplexed tool for building and testing new genetic codes in cell-free translation systems.

Radford et al. revisited a long-standing assumption that the tRNA 3′ CCA end, where amino acids attach and tRNAs dock into the ribosome, must be intact for aminoacylation. Using a new sequencing method they developed, tSCAN, the team varied the tRNA 3′ end across the entire E. coli tRNA set and found that most non-CCA tRNAs ("otRNAs") were still efficiently charged by natural synthetases, far more tolerant to mutation than previously believed.

Building on this, the authors engineered ribosomes (G2251C/G2553C, "CGA ribosomes") that specifically accommodate otRNAs while ignoring native tRNAs. Pairing otRNA pools with these orthogonal ribosomes gave rise to AGENTEX, run end-to-end on an automated OT-2 robotic platform. Using it, the team compressed the 64-codon code down to as few as 21–22 codons, incorporated a non-standard amino acid via amber suppression, and showed the compressed and standard genetic codes could run in parallel, without "crosstalk". Confirming this "zero crosstalk" required proteomics sensitive enough to catch rare mistranslation events. The team relied on PEAKS Studio 13 to search high-sensitivity LC-MS/MS data against custom libraries covering every possible amino acid substitution their engineered codes could introduce, showing that the ribosome, not the synthetase, is the real gatekeeper of genetic code fidelity.

Congratulations to the Church Lab on this remarkable accomplishment! This breakthrough technology overturns decades of understanding of how transfer RNAs (tRNAs) help turn the genetic code into proteins and takes a leap forward by making 34 codons customizable, allowing researchers to make proteins with up to 34 different amino acids much faster and safer.

BSI is delighted to witness the application of PEAKS software in this pioneering research within synthetic biology! We sincerely appreciate our ongoing collaboration with Dr. Bogdan Budnik and look forward to future advancements.

Read the full article here: Radford, F., Sapers, N., Burgess, H. M., Ort, L., Budnik, B., & Church, G. M. (2026) Automated prototyping of genetic codes. Nature. https://doi.org/10.1038/s41586-026-10949-y