From Genome Writing to Novel Polymers: Constructive Bio's and Jason Chin’s Bold Vision for Engineered Biology

Imagine biological factories capable of manufacturing any polymer you desire. Stronger than steel, more flexible than rubber, with capabilities beyond the grasp of both evolution and modern materials science. In an exclusive interview following their presentation at SynBioBeta 2025 in San Jose, Jason Chin and the Constructive Bio team unveiled their remarkable advances in genome writing and engineered translation. These innovations carry profound implications for therapeutics, sustainable materials, and beyond. Built on two decades of research from the Chin Lab, the company takes a dual approach: writing whole genomes and engineering protein translation to unlock the potential of fully programmable polymers.

“Combining deeply recoded genomes with engineered translation enables the encoded cellular synthesis of entirely new classes of polymers.  This opens up new to nature molecules with potential applications across virtually every sector, ” says Jason Chin.

Biology is a master polymer factory. Living cells string together amino acid monomers to create proteins rapidly, accurately, sustainably, and at a massive scale. Modern materials science struggles to replicate even one of these feats, let alone all four simultaneously. Instead of limiting themselves to nature's amino acids, Constructive Bio reprograms cells to produce entirely new types of polymers using non-natural monomers. This innovation opens the door to discovering materials with novel properties and chemistries.

Alongside their translation engineering efforts, the Chin Lab and Constructive Bio are developing and implementing tools for whole-genome writing. The past, present, and future of synthetic biology hinge on our ability to modify cellular DNA. As the field progresses from minor alterations (<10 kb) to engineering entire genomes (>1Mb), new tools for constructing and assembling long genomes are essential.

The technology begins with assembling large, synthetic DNA fragments that replace megabase-scale sections of an organism's natural genome. Within these synthetic DNA constructs, specific redundant genetic codons are entirely removed. This frees up those codons and their associated cellular machinery—such as tRNAs and aminoacyl-tRNA synthetases. By introducing new tRNAs and synthetases, the cell's translational system is re-purposed to recognize these free codons and assign them to entirely new, non-natural monomers. The result is a "recoded" organism capable of sustainably building unique polymers at scale, extending far beyond nature's standard 20 amino acids. These non-canonical polymers can be endowed with enhanced properties in new materials and therapeutics.

The pinnacle of this technology is Syn57, an E. coli strain recently published by the Chin Lab, representing the most advanced recoded organism ever developed. This tour de force of synthetic genomics involved reducing the genetic code from 64 to just 57 codons, a feat requiring over 100,000 precise codon replacements across its 4Mb genome. "Our work on recoding, including the synthesis of Syn57, exemplifies how we can computationally design a genome with specific properties and generate a living organism that embodies that design," Professor Chin explained. "The work on Syn57 highlights two key challenges in engineering biology: first, we need to be able to write the DNA sequences of living organisms, and second, we need to know what DNA sequences to compose so that the resulting organisms possess the desired functions.”

These recoded organisms also offer unique advantages for real-world deployment: evolutionary stability, built-in viral resistance, and a reduced risk of horizontal gene transfer. By removing redundant codons, the engineered genomes become highly sensitive to mutations, making them more evolutionarily stable. Furthermore, viral genomes and foreign genes transferred from other organisms become essentially "untranslatable" in recoded cells, creating a natural firewall against genetic contamination. These attributes provide the confidence needed for deploying engineered organisms in real-world scenarios—a persistent challenge for the practical application of synthetic biology.

The journey to Syn57 and beyond has been facilitated by genome assembly technologies developed in the Chin Lab, such as REXER and GENESIS. These tools allow for the efficient replacement of genomic sections with 100kb synthetic DNA fragments. Combined with declining DNA synthesis and sequencing costs, these advancements are democratizing the ability to assemble synthetic genomes. A process that once took months can now be achieved in days.

The applications are already materializing. "At Constructive Bio, we are already using organisms with compressed genetic codes for the discovery and scalable biomanufacture of therapeutic molecules, including highly modified peptide and protein therapeutics," stated Professor Chin. This includes next-generation therapeutics like improved versions of drugs for diabetes and weight loss, where non-canonical amino acids (ncAAs) can enhance stability and efficacy, and novel antibody-drug conjugates with precisely placed payloads.

The future for Constructive Bio and Professor Chin holds ambitions far exceeding the limits of evolution and traditional materials science. He also foresees "possibilities of using recoded cells – that cannot exchange genetic information with natural life or be infected by viruses – as a basis for potential therapies."

To accelerate these breakthroughs and tackle synthetic biology design challenges at scale, Professor Chin is leading the new Generative Biology Institute at EIT Oxford. Set to launch later this year, the institute has "sustained and substantial funding, and an ambition to apply our foundational advances for the benefit of humanity." 

Constructive Bio is not merely building on nature; it's building beyond it, forging a future where cells become programmable biofactories for a more sustainable and creative world. Their work exemplifies for many the true promise of synthetic biology: mastering the ability to write whole genomes that transcend the reach of evolution and modern technology. Creativity becomes the new limit. As they continue to expand the genetic alphabet and the toolkit of biology, the industry watches keenly, anticipating the next wave of innovation from these pioneers of genome writing.