GoKawiilA new method for writing DNA promises to unlock the potential of 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, 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 sequences.”
The advance, presented earlier this month at SynBioBeta 2026 in San Jose, Calif., and detailed in a preprint posted to bioRxiv, addresses one of the more vexing mismatches in modern genomics research. Generative AI tools like Evo 2, trained on the genetic code of millions of organisms, can design new DNA sequences on demand 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?
In a demonstration of how squarely Sidewinder targets this bottleneck, the team behind the technique, led by Caltech synthetic biologist Kaihang Wang, harnessed the power of Evo 2 to redesign a 12,500-letter DNA sequence of the E. coli 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 microbes that manufacture drugs, biofuels, or specialty chemicals, and eventually to the assembly of vast DNA constructs approaching complete artificial genomes.
In the past, says Brian Hie, the Stanford computational biologist whose lab developed Evo 2, 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 in Nature, but with substantially greater capacity.
... continue reading