Reprogrammed DNA controls living cells without altering their genes

Apr 03, 2026

Scientists used a bacterial system called retron to turn DNA into a programmable tool inside living cells, enabling gene regulation and disease detection.

(Nanowerk News) A research team at POSTECH has developed a platform that repurposes DNA from its conventional role as genetic storage into a functional tool for controlling cellular behavior in living cells. Led by Associate Professor Jongmin Kim and doctoral candidate Geonhu Lee from the Department of Life Sciences, the work was published in Nature Chemistry (“Construction of synthetic protein-binding non-genetic DNA systems in living cells”). The non-genetic DNA platform leverages a bacterial system called retron to produce programmable DNA fragments that interact with proteins and modulate cell activity without disrupting the genome.

Key Findings

Inside a cell, proteins and RNA serve as the active molecular workforce, produced on demand and broken down after completing their tasks. DNA, by contrast, has always functioned as the master blueprint directing these operations, stored safely and kept unaltered. While DNA has been used as a tool outside living cells, for example in PCR-based diagnostic tests for viral infections, introducing functional DNA inside a cell has historically forced it back into its native genetic role. The POSTECH team set out to overcome this constraint. Their solution involved engineering the retron system, a naturally occurring bacterial mechanism that synthesizes DNA through reverse transcription. Unlike conventional DNA replication, which copies directly from existing DNA templates, the retron pathway reads an intermediate RNA molecule and generates new non-genetic DNA from it. The fragments produced through this process remain stable and independent from the cell’s genomic DNA, free to carry out programmable tasks. Schematic illustration of the intracellular production of protein-binding non-genetic DNA and its application in controlling protein activity. (Image: POSTECH) Through this approach, the researchers generated non-genetic DNA fragments with specific, designed functions directly inside living cells. These fragments bind to target proteins and alter cellular behavior without compromising the integrity of the cell’s genetic information. “We have provided the necessary framework to open up a whole new design space that unfetters DNA from its role as ‘genetic material,'” said Geonhu Lee, the doctoral candidate who led the study. The team demonstrated three synthetic biology applications for the technology. First, DNA fragments served as molecular decoys to attract specific proteins and regulate gene expression. Second, the fragments enabled real-time control over where proteins localize within the cell and how they function, triggered by the detection of specific signals. Third, the platform recorded brief molecular events semi-permanently, allowing transient signals to be captured and stored as lasting cellular records. The implications reach beyond existing DNA-based circuit designs. Capturing and recording fleeting disease markers in real time, such as indicators of cancer or inflammation, could provide a foundation for developing autonomous smart biotherapeutics capable of self-regulating therapeutic responses. Engineered living biosensors built on this non-genetic DNA platform could also detect environmental pollutants, including microplastics and heavy metals. Professor Jongmin Kim added, “We now have access to a foundational technology that can potentially be used to revolutionize multiple application areas, including medicine, environment, and energy.” By decoupling DNA from its genetic function and converting it into a programmable cellular agent, the retron-based platform gives synthetic biologists a concrete new mechanism for building responsive, autonomous living systems.