Publications
Peer-reviewed research from Constructive Bio on whole-genome recoding, genetic code expansion, and site-specific ncAA incorporation in peptides and proteins.
Sense Codon Reassignment Enables Virus-Resistant Production Strains and Encoded Non-Natural Polymer Synthesis
Robertson, W.E., Funke, L.F.H., de la Torre, D., Fredens, J., Elliott, T.S., Spinck, M., Christova, Y., Cervettini, D., Böge, F.L., Liu, K.C., Buse, S., Maslen, S., Salmond, G.P.C., Chin, J.W. Science 372(6546), 1057–1062 (2021)
Sense codon reassignment in recoded E. coli simultaneously enables two commercially valuable capabilities: inherent resistance to viral infection and the encoded synthesis of non-natural polymers with properties not found in biological systems. The virus resistance eliminates a major contamination risk in industrial fermentation, while polymer synthesis demonstrates the platform's potential beyond therapeutics into advanced biomaterials.
Read more →Key publications
Syn61: Total Synthesis of E. coli with a Fully Recoded Genome - The Foundation of Constructive Bio's Platform
Fredens, J., Wang, K., de la Torre, D., Funke, L.F.H., Robertson, W.E., Christova, Y., Chia, T., Schmied, W.H., Dunkelmann, D.L., Beránek, V., Uttamapinant, C., Gonzalez Llamazares, A., Elliott, T.S., Chin, J.W.
Nature 569(7757), 514–518 (2019)
Why it matters: Syn61 is the origin of Constructive Bio's programmable biology platform. By proving that an organism can survive with a compressed genetic code, this work created the 'blank codons' that Constructive Bio's BioForge platform now uses to encode non-canonical amino acids into peptide therapeutics at industrial scale. Every subsequent advance, from multi-ncAA incorporation to virus-resistant production strains, builds directly on Syn61.
Engineered triply orthogonal pyrrolysyl–tRNA synthetase/tRNA pairs enable the genetic encoding of three distinct non-canonical amino acids
Dunkelmann, D.L., Willis, J.C.W., Beattie, A.T., Chin, J.W.
Nature Chemistry 12(6), 535–544 (2020)
Why it matters: One of the key enabling steps toward multiplexed ncAA incorporation and the programmable synthesis of chemically richer biomolecules.
REXER and GENESIS: The Genome Writing Toolkit for Creating Custom Synthetic Genomes in E. coli
Robertson, W.E., Funke, L.F.H., de la Torre, D., Fredens, J., Wang, K., Chin, J.W.
Nature Protocols 16, 2345 (2021)
Why it matters: REXER and GENESIS are the 'how' behind Constructive Bio's genome synthesis capability. They enable the precise, large-scale rewriting of bacterial genomes that produces the company's recoded production organisms. Having a published, validated protocol in Nature Protocols demonstrates the robustness and reproducibility of the approach that underpins the BioForge platform.
White papers
Genome synthesis: how to write a genome at scale
Genome synthesis is the ability to write DNA at the scale of entire chromosomes and genomes. It is fundamentally different from gene editing, and it enables applications that editing cannot reach.
Genetic code expansion: how recoded genomes unlock new biology
Genetic code expansion uses whole-genome recoding to free up codons and assign them to amino acids that biology has never used, opening new routes to drug discovery and sustainable manufacturing.
Non-canonical amino acids and programmable biomolecules
Non-canonical amino acids expand the building blocks of biology beyond nature’s standard set, enabling programmable peptides, proteins, macrocycles, and polymers with properties not found in nature.
24 recent non-canonical amino acid breakthroughs
A roundup of 24 non-canonical amino acid advances published in 2025, spanning oncology, drug delivery, enzyme engineering, antimicrobials, gene therapy, and materials science.
Selected publications
Genetic Code-Locking Gives Recoded Organisms Stable Virus Resistance, Eliminating a Key Biomanufacturing Risk
Zürcher, J.F., Dickson, A., Kappes, T., Kleefeldt, A.A., Liu, K.C., Salmond, G.P.C., Chin, J.W.
Biochemistry 64, 3093 (2025)
Genetic code-locking confers stable virus resistance to recoded organisms. Because viruses depend on the host cell's standard genetic code to replicate, organisms with refactored codes become inherently resistant to viral infection. This research demonstrates that the resistance is stable over many generations, addressing one of the most significant contamination risks in industrial biomanufacturing where viral outbreak can destroy entire fermentation batches of peptide therapeutics.
Read more →Automated Orthogonal tRNA Generation Removes a Key Bottleneck in Scaling Non-Canonical Amino Acid Incorporation
Spinck, M., Guppy, A., Chin, J.W.
Nature Chemical Biology 21, 657 (2024)
Automated generation of orthogonal tRNAs for genetic code expansion. Orthogonal tRNAs are essential components for incorporating non-canonical amino acids into proteins, but creating them has been a manual, time-consuming bottleneck. This automated approach accelerates the development of new tRNA/synthetase pairs, enabling faster expansion of the ncAA toolbox available for engineering peptide therapeutics with enhanced properties through Constructive Bio's fermentation-based manufacturing platform.
Read more →Non-Standard Backbone Chemistries Added to the Genetic Code of a Living Organism for Enhanced Peptide Therapeutics
Dunkelmann, D.L., Piedrafita, C., Dickson, A., Liu, K.C., Elliott, T.S., Fiedler, M., Bellini, D., Zhou, A., Cervettini, D., Chin, J.W.
Nature 625, 603 (2024)
The incorporation of α,α-disubstituted and β-linked monomers into the genetic code of a living organism. These non-standard backbone chemistries produce peptides with fundamentally altered structural properties including enhanced resistance to proteolytic degradation — a critical limitation of conventional peptide therapeutics. This work directly enables Constructive Bio's platform to produce next-generation peptide drugs with longer half-lives and improved oral bioavailability through fermentation-based manufacturing.
Read more →Megabase-Scale Genome Synthesis: Continuous Assembly of E. coli Sections and Human DNA at Unprecedented Scale
Zürcher, J.F., Kleefeldt, A.A., Funke, L.F.H., Birnbaum, J., Fredens, J., Grazioli, S., Liu, K.C., Spinck, M., Petris, G., Murat, P., Rehm, F.B.H., Sale, J.E., Chin, J.W.
Nature 619, 555 (2023)
Continuous synthesis of E. coli genome sections and megabase-scale human DNA assembly. This research demonstrates that entire genome sections can be synthesised and assembled continuously at megabase scale, establishing the large-scale DNA writing capabilities that underpin Constructive Bio's synthetic genomics platform and its collaborations in genome engineering including the Ellison Institute's Generative Biology Institute.
Read more →Five Mutually Orthogonal tRNA Systems Enable Up to Five Distinct Non-Canonical Amino Acids in a Single Protein
Beattie, A.T., Dunkelmann, D.L., Chin, J.W.
Nature Chemistry 15, 948 (2023)
Quintuply orthogonal pyrrolysyl-tRNA synthetase/tRNA pairs that enable the simultaneous incorporation of up to five distinct non-canonical amino acids into a single protein. Each tRNA/synthetase pair operates independently without cross-reactivity, providing the most advanced multi-ncAA incorporation capability demonstrated to date. This directly answers the pharmaceutical industry question of how many different ncAAs can be incorporated into a single therapeutic peptide or protein using Constructive Bio's platform.
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