Programmable nanorobots made of DNA

It is the nanotechnological vision: tiny little robots performing highly specific tasks in the human body, such as delivering pharmaceutical agents or repairing defective cells. Such programmable nanosystems could lay the foundations for smart molecular machines that complete a whole range of tasks from drug delivery to molecular data processing. Although there is still a long way to go before this becomes reality, a team led by Professor Philip Tinnefeld, leader of the NanoBioSciences research group at LMU’s Faculty of Chemistry and Pharmacy and member of the BioSysteM Cluster of Excellence, has taken an important step. Using the so-called DNA origami method, the researchers have developed a robot system made of DNA molecules which, for the first time, can be programmed like a computer chip. Another novel aspect of the system is that the energy powering it does not come from outside, but is stored in molecular tensions inside the DNA structure.

For some years now, DNA origami has been viewed as a key technology for building molecular machines. It involves folding a long strand of DNA with the aid of many shorter strands into a precisely defined three-dimensional form. This makes it possible to build nanometric structures which alter their shape under certain conditions – by opening, for instance, or closing, or rotating. “These are systems that interact with the environment by reacting to certain stimuli, whether that be light, temperature, pH levels, or enzymes,” explains Tinnefeld. Once the inputs reach a certain threshold, the nanobot performs an action. As examples, he cites: “It might emit a molecule that interacts with a cell – perhaps killing it because it is diseased. Or it might release a strand of DNA which changes the gene expression of the cell and steers it in a healthy direction.”

Network of molecular ‘flip switches’

Most previous approaches have worked according to a simple on-off principle: A single stimulus changes the structure of the folded DNA, and that is it. The new invention, which goes by the name of SEPP (Serial Execution of Programmable Processes), goes a step further. It combines several of these little switches into a network. “The switches are placed in the DNA origami that can ‘fold over’ under certain energy conditions,” says Tinnefeld. “We incorporate a ‘lock’ into each of the switches, which block them in the first instance. The locks define possible interactions with the environment.” For example, they can interact with nucleic acids, antibodies, enzymes, or light. “Depending on whether and to what extent a stimulus is present, the lock opens and the corresponding structure folds over,” adds the professor of physical chemistry.

Tinnefeld compares this principle to a computer: “The DNA structure is effectively the hardware. And the various locks that determine how the robot reacts to its environment form the software.” The researchers even managed to incorporate a time delay into their switches. This makes it possible to specify the sequence and the timing of actions – like a program with multiple commands. One possible scenario: If a certain enzyme becomes active and then light of a special wavelength strikes the area, the nanorobot carries out a defined action. For example, it could start to glow, release a molecule, or launch a chemical reaction.

Tinnefeld and his team are already working on a computing system that does not require any stored energy: “The nanorobot interactions themselves supply enough energy for the computing processes,” he explains. Brownian DNA computing is the name given to the underlying principle, which uses the random thermal movement of molecules (Brownian motion) to power computing processes. “In the BioSysteM Cluster of Excellence, which is due to launch in January 2026, we will pursue further research into such approaches,” says Tinnefeld. And so, bit by bit, the vision of autonomous, smart nanorobots could become reality.

Martina Pfeiffer et al.: Spring-loaded DNA origami arrays as energy-supplied hardware for modular nanorobots. Science Robotics 2025