DNA built without a template

DNA is usually copied from an existing strand, like tracing text on a page. A March 2026 study reported that some DNA-copying enzymes can also build new DNA without that template, and that researchers can steer the output with temperature and chemistry. (nature.com) The paper, published February 26, 2026 in *Nature Communications*, was led by Simeon D. Castle and Thomas E. Gorochowski with co-authors from the University of Bristol, the Medical Research Council Laboratory of Molecular Biology, and other institutions. The team tested natural and engineered DNA polymerases with long-read nanopore sequencing, fluorescence assays, and atomic force microscopy. (nature.com) DNA polymerases are the enzymes cells use to copy genetic material, and most need a template strand to tell them which letter to add next. The Bristol group examined a lesser-known behavior, documented since the 1960s, in which some polymerases make single-stranded DNA fragments with no template at all. (nature.com) The researchers call that behavior “untemplated” synthesis, and the paper says it can produce pools of DNA fragments whose sequence patterns shift when buffer conditions and temperature change. The study says those changes could support “guided synthesis” of DNA sequences on the kilobase scale, meaning lengths in the thousands of bases. (nature.com; bristol.ac.uk) That is different from the standard way most synthetic DNA is still made in labs and factories. A 2018 *Nature Biotechnology* paper noted that phosphoramidite chemistry, the dominant chemical method, is generally limited to direct synthesis of about 200-base strands and produces hazardous waste. (nature.com) Scientists have been trying to replace or supplement that chemistry with enzyme-based methods for years. A 2019 *Nature* news feature described enzymatic DNA synthesis as an alternative that was moving closer to practical use, and a 2023 *Science Advances* paper showed single-base control in a parallel enzymatic system built around terminal deoxynucleotidyl transferase, or TdT, a template-free polymerase. (nature.com; science.org) The new 2026 paper does not report a desktop machine that can write any chosen genome from scratch on demand. It reports that untemplated activity is widespread across polymerases, that the resulting DNA has measurable motif biases, and that those biases can be shifted by changing reaction conditions. (nature.com) The University of Bristol said the work showed for the first time that this “doodling” activity could be steered and controlled. In the paper itself, the authors frame the result more cautiously, saying the data “may support” repurposing untemplated polymerase activity for guided synthesis of long DNA sequences. (bristol.ac.uk; nature.com) The distinction matters for anyone reading social posts that describe the work as DNA being built “from scratch.” The paper supports that phrase in the narrow sense that no template strand was provided, but it does not show precise, arbitrary sequence writing at the level needed for routine gene manufacturing. (nature.com; science.org) What happens next is likely to be less about whether template-free DNA synthesis exists and more about control. The open question, after this February 2026 paper, is how far researchers can push that control from biased sequence pools toward reliable writing of long, specified DNA strands. (nature.com)