A ‘smart’ DNA-based system that precisely identifies cancer cells and releases drugs only at the tumour site has been developed by researchers at the University of Geneva (UNIGE) in Switzerland. 

A major challenge in oncology today is targeting cancer cells without damaging healthy surrounding tissue. The research team at UNIGE has developed a ‘smart’ drug based on synthetic DNA strands that can do just that, in a process similar to two-factor authentication on a banking website.

While there are currently methods capable of delivering drugs precisely to cancer cells – antibody-drug conjugates being the most promising – they face limitations such as poor tissue penetration, large size and restricted drug payload capacity.

In comparison, UNIGE’s new DNA-based technology offers advantages as the DNA components are relatively small, can move through tumours more easily and deliver higher drug concentrations.

The way it works is that the system’s independent DNA strands carry distinct components, including two different cancer-targeting binders and a cytotoxic drug. When it detects two specific cancer biomarkers on the surface of a diseased cell, the DNA strands assemble like a puzzle. This triggers a chain reaction that releases the drug into the centre of that cell while sparing neighbouring healthy cells as much as possible. 

Similar to two-factor authentication, this process only occurs when both cancer markers are present. If either marker is missing, the chain reaction cannot initiate and the drug remains inactive.

“Until now, computers and AI have helped us design new drugs. What’s new here is that the drug itself can, in a simple way, ‘compute’ and respond intelligently to biological signals,” said Nicolas Winssinger, full professor in the department of organic chemistry at UNIGE and last author of the study.

He explains that just as computers are built on simple logic operations – ‘and’, ‘or’, ‘not’ – this technology applies the same principle at the molecular level. In their study, an ‘and’ logic gate ensures activation only when two cancer biomarkers are present, making the drug highly selective.

During lab tests, the technology was able to successfully identify cancer cells with specific combinations of surface proteins and selectively deliver potent drugs, while nearby healthy cells remained unharmed. The researchers also demonstrated that multiple therapeutics can be combined within the same treatment, a strategy that may help prevent or overcome drug resistance.

“This research could mark an important step forward in the evolution of medicine, with the introduction of a self-operating drug system,” said Winssinger.

According to the team, their research paves the way for autonomous and programmable drug delivery. Future systems could integrate additional logic operations, creating medicines capable of complex decision-making inside the body. If ‘smart’ drugs are able to adapt to their environment, treatment can be tailored to each patient’s unique physiology while minimising side effects.

The study – DNA-drug conjugates enable logic-gated drug delivery amplified by hybridisation chain reactions – has been published in the journal Nature Biotechnology.