Leap in DNA synthesis slashes time to build new genetic sequences

A new DNA synthesis method called Sidewinder can assemble dozens of genetic sequences simultaneously in a single test tube with just one error per 10 million assembly events, far surpassing conventional methods. Developed by Caltech synthetic biologist Kaihang Wang and colleagues, the technique enabled the team to use generative AI tool Evo 2 to redesign a 12,500-letter DNA sequence and build it from scratch with no errors. The advance, presented at SynBioBeta 2026 and detailed in a preprint, addresses a critical bottleneck in genomics where AI can design DNA sequences faster than scientists can physically construct them.

A new method for writing DNA promises to unlock the potential of generative AI https://spectrum.ieee.org/tag/generative-ai in biology, giving scientists a fast, affordable, and accurate way to physically build the novel genetic sequences that predictive models are now producing faster than anyone can construct them. The technique, called Sidewinder, can assemble dozens of genetic sequences simultaneously in a single test tube, producing just one incorrect junction for every 10 million assembly events—a level of precision that far surpasses conventional methods, which misfire roughly once every 10 to 30 joins. Sidewinder also draws on cheap raw materials that have until now been too difficult to use reliably. “It’s a step change,” says Thomas Gorochowski https://www.bristol.ac.uk/people/person/Thomas-Gorochowski-a612576a-e38a-47aa-bbb6-c79a3126f5be/ , a bioengineer at the University of Bristol, in England, who was not involved in the research. “It really opens up the feasibility of synthesizing large genetic systems, maybe even small genomes.” And that, he adds, “is uber-important for all of the AI stuff that’s coming out at the moment around generative genome https://spectrum.ieee.org/tag/genome sequences.” The advance, presented https://www.syntheticbiologysummit.com/2026-speakers/kaihang-wang?gclid=Cj0KCQjw2MbPBhCSARIsAP3jP9xOmPZuVh6zGZ4shlq8dx-NagHU9R7slxbWkg0zNrgR3dHwpwg9IF8aAuBSEALw wcB earlier this month at SynBioBeta 2026 in San Jose, Calif., and detailed in a preprint posted https://www.biorxiv.org/content/10.64898/2026.05.01.722326v1 to bioRxiv , addresses one of the more vexing mismatches in modern genomics https://spectrum.ieee.org/tag/genomics research. Generative AI tools like Evo 2, trained on the genetic code of millions of organisms, can design new DNA sequences on demand https://spectrum.ieee.org/synthetic-biology-ai-adrian-woolfson at extraordinary speed. But physically constructing long DNA sequences in a laboratory has remained slow and expensive, especially when building not just one sequence at a time but dozens of different designs simultaneously, as testing AI predictions at scale demands. RELATED: Can Biologists Rewrite the Genome’s Spaghetti Code? https://spectrum.ieee.org/synthetic-biology-ai-adrian-woolfson In a demonstration of how squarely Sidewinder targets this bottleneck, the team behind the technique, led by Caltech https://spectrum.ieee.org/tag/caltech synthetic biologist Kaihang Wang https://www.bbe.caltech.edu/people/kaihang-wang , harnessed the power of Evo 2 to redesign a 12,500-letter DNA sequence of the genome in silico and then used Sidewinder to build it from scratch—with no errors. Sequences of that length can encode entire biochemical pathways, laying the groundwork for engineered E. coli https://spectrum.ieee.org/tag/e-coli microbes https://spectrum.ieee.org/tag/microbes that manufacture drugs, biofuels https://spectrum.ieee.org/tag/biofuels , or specialty chemicals, and eventually to the assembly of vast DNA constructs approaching complete artificial genomes. In the past, says Brian Hie https://profiles.stanford.edu/brian-hie , the Stanford https://spectrum.ieee.org/tag/stanford computational biologist whose lab developed Evo 2 https://www.nature.com/articles/s41586-026-10176-5 , a project like this would likely take more than a month, based on his team’s experience with conventional commercial methods. “With a technology like this,” he says, “you could probably achieve the same thing in a few days.” To commercialize Sidewinder, from left Noah Robinson, Kaihang Wang, Adrian Woolfson, and Brian Hie cofounded a company called Genyro. Marcus Ubungen A New Assembly Logic The new method builds on a DNA synthesis strategy that Wang and his colleagues first outlined at the beginning of the year https://www.nature.com/articles/s41586-025-10006-0 in Nature , but with substantially greater capacity. Thanks to a new algorithm that automates the most computationally demanding part of the process and laboratory innovations in how raw ingredients are managed, it is now feasible to synthesize ever larger and more numerous DNA constructs simultaneously. This opens up applications including drug discovery https://spectrum.ieee.org/tag/drug-discovery , data storage https://spectrum.ieee.org/dna-data-storage , and the design of synthetic organisms https://spectrum.ieee.org/launched-a-factory-for-making-weird-new-organisms . “The pace at which you can start to explore these things just opened up massively,” Gorochowski says. To understand how Sidewinder works, it helps to understand how DNA is typically made in a laboratory. The process begins with short, chemically manufactured strands called oligonucleotides, or oligos, the molecular alphabet blocks from which longer sequences are assembled. Ordering oligos individually is reliable but expensive. Scientists discovered years ago that they could slash costs by synthesizing thousands of different oligos together in a single pool. But doing so creates a chaotic soup in which fragments tangle with unintended partners, leading to errors. Sorting out specific sequences from such a pool has traditionally required elaborate separation steps: physically dividing up the fragments, isolating them in tiny droplets, or fishing them out one by one with laser light. Each approach added cost, time, and specialized equipment. The Caltech team sidestepped the problem entirely. Page Numbers for DNA Sidewinder also starts with oligos, the kind anyone can buy from DNA synthesis vendors such as GenScript https://www.genscript.com/ or Twist Bioscience https://www.twistbioscience.com/ , but tags each fragment with a unique molecular barcode. This short identifying sequence ensures that each piece links up only with its intended neighbor in the order that will yield the desired genetic sequence. When two bar-coded fragments meet, they form what chemists call a three-way junction: a fleeting molecular knot that locks the pieces in alignment before being cleanly removed, leaving a seamless strand. Wang likens these barcodes to page numbers. Whereas conventional assembly is like collating an unnumbered manuscript by matching the last line of one page to the first line of the next—workable for a short document, a recipe for chaos when sequences repeat—Sidewinder’s barcodes guide each fragment to its correct partner regardless of what sequence it carries. The original Sidewinder protocol required a computationally intensive calculation to design those barcodes, however, and this became impractically slow as the number of fragments grew. A former Caltech undergraduate student named Jean-Sebastien Paul https://profiles.stanford.edu/jean-sebastien-paul developed a workaround. While working in Wang’s lab one summer, Paul, who is now pursuing a Ph.D. at Stanford, built a software tool called PyWinder that churns out the barcodes in minutes on a standard laptop, replacing a calculation that had previously been too slow to scale. Bioengineer Noah Robinson https://wanglab.caltech.edu/people/noah-robinson , a postdoc in Wang’s lab who codeveloped the original Sidewinder method, also adapted the approach to work from cheap, mass-produced DNA ingredients, further cutting time and cost. Wang and Robinson, together with Hie and entrepreneur Adrian Woolfson https://adrianwoolfson.com/about/ , cofounded a company called Genyro https://www.genyro.com/ —to commercialize the technology, hoping to turn a profit through paying pharmaceutical https://spectrum.ieee.org/tag/pharmaceutical and biotech clients. According to Robinson, however, they intend to make the Sidewinder platform broadly accessible to the academic research community. “We really want this to be an enabling platform,” says Robinson. “We want people to do cool things with the technology.” Elie Dolgin https://spectrum.ieee.org/u/elie-dolgin Elie Dolgin http://www.eliedolgin.com/ is a science writer specializing in biomedical research and drug discovery. After a PhD spent studying the population genetics of nematodes, he swapped worms for words—entering journalism as an editor at The Scientist , Nature Medicine , and STAT . Now a freelancer, Elie is a frequent contributor to New Scientist , Nature , IEEE Spectrum , and more.