KAIST develops world-first DNA synthesis technology using temperature alone

The joint research team behind the study. From left: Park Seong-jun, KAIST researcher; Kim Woo-jin, GIST integrated master's-doctoral student; Kim Jin-ho, GIST doctoral student; Choi Jang-ho, KAIST researcher; Choi Young-jae, KAIST professor; Ryu Tae-hun, CEO of ATG LifeTech; Lee Chae-rim, senior researcher at ATG LifeTech; and Choi Han-sol (top right), professor at Ewha Womans University. [Provided by KAIST]

South Korean researchers have upended a long-held assumption in biology — that synthesizing DNA requires complex chemical processes — by developing a platform that builds DNA sequences using temperature control alone, without swapping out chemical reagents.

KAIST announced Tuesday that a research team led by Professor Choi Young-jae of its Graduate School of Engineering Biology, working jointly with ATG LifeTech and a team led by Professor Choi Han-sol of Ewha Womans University, had developed the foundational platform technology.

DNA serves as the blueprint carrying the genetic information of all living organisms, including humans. Scientists synthesize custom DNA sequences to diagnose diseases, develop new drugs and engineer microorganisms with novel functions. Until now, however, producing DNA required repeatedly adding and washing away chemical reagents each time one of the four nucleotide bases — A, T, G and C — was attached in sequence, a process that demanded automated synthesis equipment costing hundreds of millions of won and specialized research facilities.

To overcome these limitations, the team developed hairpin DNA that reacts only at specific temperatures. Hairpin DNA is a specialized structure that folds like a hairpin and unfolds only when exposed to a set temperature.

The researchers loaded multiple types of hairpin DNA — each designed to activate at a different temperature — into a single test tube, then synthesized a target DNA sequence step by step simply by changing the temperature in a set order.

A schematic diagram of the research findings. [Provided by KAIST]

Where conventional DNA synthesis requires continuous reagent changes, the new method loads all necessary materials into a single test tube from the outset and assembles the target sequence simply by adjusting the temperature. The approach opens a path to synthesizing DNA with nothing more than a standard temperature-control device, eliminating the need for complex reagent handling or large-scale equipment.

To demonstrate real-world applicability, the team also built a battery-free "DNA temperature black box." The device is stored in a freeze-dried state and activates with a single drop of water just before use. It then automatically records in its DNA sequence when, how much and in what order temperatures changed during delivery. It also changes color when exposed to temperatures above a set threshold, allowing users to visually confirm any anomaly — a feature the researchers expect to prove useful for quality control of products requiring cold-chain management, including vaccines, biopharmaceuticals, cell therapies and fresh food.

"We succeeded in synthesizing a desired DNA sequence inside a single test tube using only a standard temperature-control device — a new paradigm that dramatically lowers the complexity and cost of DNA synthesis," Choi said. "We expect this to reduce barriers to entry in basic biotech research by making DNA synthesis easier and more economical, and to open new industrial applications such as the battery-free DNA temperature black box."

The findings were published in the international journal Nature Communications on July 2.

nbgkoo@heraldcorp.com