Scientists have described a DNA synthesis method in Nature that could change how DNA is written, potentially allowing researchers to build genetic sequences from scratch rather than piecing them together by modifying existing strands.
The new approach, called Sidewinder, creates a three-way DNA junction rather than relying on the two-way junctions used in traditional synthesis. This additional junction stores complex construction information without needing to be part of the finished sequence, giving engineers unprecedented control over DNA assembly.
Molecular biologist and Genyro CEO Adrian Woolfson described Sidewinder’s impact on design: “Fundamentally this enables you to turn DNA into a programmable material and into a predictive engineering material.”
Researchers demonstrated the technique by assembling the native coding sequence of apolipoprotein E (APOE), a protein crucial for regulating cholesterol transport.
Kaihang Wang, an inventor of the technology and assistant professor at Cal-Tech, likened the challenge of DNA assembly to arranging pages in a book: “In order to have a book, not only do we need to have the printed each individual page, you also need to arrange them into the correct order to form the book, right? And before us, DNA construction is kind of like in the era of you have the printing press, but you don’t have the another thing called a page number to actually align and assemble the books in the right order.”
Woolfson said the innovation bridges a long-standing gap between DNA design and construction: “Essentially, we’re democratising the process of DNA assembly, or construction if you prefer to call it construction. And this really frees up scientists and the biopharmaceutical industry to build anything that they like. Until now, there’s been a big disconnect between the ability to design DNA using AI and the ability to construct it. And this technology really kind of bridges that gap and enables the kind of feedback cycle between design, construct, test feedback.”
For the pharmaceutical industry, this could unlock capabilities for building organisms that are currently only theoretical, not physically synthesised in labs. “What we’re able to do now with this new technology is reimagine genomes from first principles,” Woolfson said, “So we go beyond the tree of life and enter the forest of possible life. And within the forest of possible life lie all kinds of incredible therapeutics, which would never have been realisable without a technology that can write them de novo.”
The researchers acknowledged the dual-use concern. Woolfson warned, “With tremendous power comes tremendous responsibility, which is why we’re considerably invested in ensuring that that this technology is used safely and that we’re able to screen sequences to ensure that the no biohazard issues associated with them.”
This breakthrough aligns with broader industry efforts to advance DNA synthesis, where the goal is to make gene writing faster, more reliable and accessible to a wider range of labs and companies.
The implications extend beyond basic research. If genetic sequences can be reliably constructed from first principles, drug discovery, therapeutic development and synthetic biology could all accelerate significantly.
As with any foundational tool in biotechnology, oversight and safety will be critical to ensure these powerful capabilities are deployed ethically and securely.
Author: Kieran Seymour