Researchers at Aarhus University have developed a microscopic DNA needle that can deliver molecules directly into cells − and, crucially, help make sure they remain active once they get there. That addresses a major problem in modern medicine: much of what enters a cell is quickly sealed off in tiny bubbles and put out of action before it ever reaches its target.
Viruses are experts at breaking into cells. They land on the cell surface, insert a needle-like structure into the membrane, and deliver a copy of their genetic material into the cell interior.
Now researchers at Aarhus University have tried to borrow that trick from nature. They have created an artificial version of a bacteriophage − a type of virus that infects only bacteria. Their synthetic version differs from the real thing in several important ways.
It carries no genetic material to inject into a cell. Instead, it can carry a payload of tailor-made molecules and release them directly inside the cell.
And rather than targeting only bacteria, it can be programmed to seek out specific cell types and deliver its payload to them.
In one crucial respect, however, it behaves like a real virus.
The molecules delivered by the needle are able to reach the inside of the cell and carry out their task. They are not neutralised by the cell’s defence system, which normally traps incoming molecules in endosomes − membrane-bound compartments in the gel-like fluid between the cell membrane and the nucleus.
That ability to avoid endosomal trapping could turn out to be the real breakthrough behind the new DNA needle.
It is a well-known problem that most medicines taken up by cells never reach their targets inside them because they are trapped and broken down.
In modern treatments for rare genetic disorders, for example, cells are made to take up oligonucleotides − short strands of DNA or RNA delivered as nanoparticles. Yet only about one per cent of those molecules escape into the cell where they are actually needed.
So far, the researchers have succeeded in getting the artificial bacteriophages to deliver a dye payload inside breast cancer cells.
That is worth stressing: this was done in the laboratory. The study is a proof of concept, showing that the method can work.
“We have not yet succeeded in getting large molecules into the cell with this method. That is the next big step, and it will be a milestone in determining whether the method can be used medically. Right now, we are actively seeking funding to continue the study,” says Professor Kurt Vesterager Gothelf of Aarhus University. He is the senior author of the study, which has been published in Advanced Science .
The researchers used breast cancer cells in the study for practical reasons connected to antibodies and receptors.
In principle, the method could be used in many different diseases where oligonucleotides or proteins need to be delivered into cells.
Kurt Gothelf expects the method to be very expensive at first, so its earliest use would most likely be in patients with rare genetic disorders that would otherwise kill them at a young age.
“But in the longer term, if it can be produced more cheaply, it could be extended to many other treatments, including cancer,” says Assistant Professor Mette Galsgaard Malle, another of the key researchers behind the study.
It will probably be a long time before the new DNA needle is ready for use in human cells.
Besides the challenge of delivering large molecules, the researchers still need to investigate how efficiently the needle gets molecules into cells, and whether such an artificial bacteriophage could trigger immune reactions in humans − or perhaps even prove toxic.
An additional protective outer layer will probably have to be added if or when the technology is to be used in humans.
That extra layer is unlikely to be a major obstacle. The artificial bacteriophage is built from modules that can be swapped depending on the type of cell being targeted and the payload it is meant to carry.
It works a little like a set of building blocks − except that it assembles itself. The researchers programme small pieces of DNA to fold into the desired scaffold and attach the other molecules needed for the task at hand. This is known as DNA origami.
“All of those functional units are important for achieving exactly the function we want. If, for example, it does not have the cleavable ends on the part of the needle that enters the cell to deliver the payload, then it does not deliver anything. At the same time, we now have a platform for investigating which units are needed to construct a specific delivery method,” says Mette Galsgaard Malle.
Mette Galsgaard Malle was not involved in the project from the start.
She was brought in at a point when the project had effectively stalled. Kurt Gothelf’s group had not been able to prove that they were actually getting anything into the cell.
Mette could. She specialises in imaging and single-particle tracking inside cells, and by using HILO microscopy she was able to follow how the dye molecules moved inside the cells.
Advanced Science
Bacteriophage-Mimetic DNA Origami Needle for Targeted Membrane Penetration and Cytosolic Cargo Delivery
9-Jan-2026
The authors declare no conflicts of interest.