Imagine if we could send tiny robotic explorers into our cells – harmless nanoscale molecules that roam around, gather clues, and report back on what they find. A team led by Peng Yin Ph.D. at Harvard University, an NIH Director’s High-Risk, High-Reward Research (HRHR) Pioneer Award recipient, is beginning to do just that. Using the building blocks of DNA, the researchers developed a new kind of molecular robotic tool that can move through a cell and collect information about how proteins are arranged. Though in its early days, this breakthrough robotics system could help researchers better understand how cells work, how diseases develop, and how medical treatments might be improved.

The researchers tested their new tool in a mammalian cell system, where proteins of interest are tagged with a short, unique DNA sequence called a probe. Tiny programmable strands of DNA called crawlers are then added to the sample. Like Velcro, the crawlers recognize and attach to the probes, one crawler for each probe. Once attached, crawlers begin copying the sequence of the probe into a growing strand. After detaching from the first probe, the crawler moves to another nearby probe and repeats the process. Over time, the crawler builds a molecular record of its journey, providing the researcher with insight into molecular arrangements inside the system. This record could be important for uncovering which proteins are close together in the cell or for counting the subunits of a protein. 

Down the line, a system like the one developed by Dr. Yin’s group could be important for molecular diagnostics: the crawlers could act like nanoscopic scouts, identifying protein-level abnormalities associated with diseases such as Alzheimer’s disease or cancer. This could lead to earlier, more accurate disease diagnosis and treatments specifically tailored to each patient. This system could also improve understanding of how drugs interact with their targets, resulting in safer, faster drug development. Though this technology is in its early stages, it is an important step forward into a new frontier of nanoscale biological exploration.

Woo, S., Saka, S.K., Xuan, F., Yin, P. Molecular robotic agents that survey molecular landscapes for information retrieval. Nature Communications, 15, (2025). https://pmc.ncbi.nlm.nih.gov/articles/PMC11024175/