UNIGE’s team has engineered a molecular system that identifies and neutralizes cancer cells with unprecedented precision, paving the way for autonomous and self-regulating drugs.
How can we target cancer cells without damaging healthy tissue? This is one of the big challenges facing oncology today. Using synthetic DNA strands, a team at the University of Geneva (UNIGE) has developed a “smart” system that can recognize cancer cells with great precision and release powerful drugs only where they are needed. Beyond cancer treatment, this research paves the way for “smart” medicines and programmable drug delivery. The full article is available in the latest issue. nature biotechnology.
The ability to directly target tumor cells with drugs could transform cancer treatment, preserve healthy tissue, and reduce the severe side effects associated with chemotherapy. Among the most promising approaches in recent decades are antibody-drug conjugates (ADCs), which use monoclonal antibodies to precisely deliver therapeutic agents to cancer cells. Despite their remarkable success, ADCs still face significant limitations, such as poor tumor tissue penetration and limited ability to deliver drug payloads.
To address this problem, researchers at UNIGE have developed a new technology based on DNA strands. Because these DNA components are relatively small, they can move through tumors more easily than traditional antibody-based therapies. Traditional antibody-based therapies are more bulky and can be limited in the number of drug molecules they can transport.
more targeted and effective
In this new system, independent DNA strands carry different components, including two different cancer target binding agents and a cytotoxic drug. When two specific cancer markers bind to their respective DNA-binding binders, the components self-assemble precisely at the tumor site. This assembly allows multiple DNA fragments to be amplified by joining together at desired locations, allowing for the delivery of higher concentrations of drug. Similar to two-factor authentication for banking websites, this process only occurs if both cancer markers are present. If either marker is missing, the hybridization chain reaction cannot be initiated and the drug remains inactive.
In laboratory studies, the technique was successful in identifying cancer cells with specific combinations of surface proteins and selectively delivering potent drugs, while leaving nearby healthy cells unharmed. Researchers also demonstrated that multiple treatments can be combined within the same treatment, a strategy that may help prevent or overcome drug resistance.
This could be an important step in the evolution of medicine with the introduction of self-manipulating drug systems. In the past, computers and AI have helped design new drugs. What is new here is that the drugs themselves can “compute” biological signals in a simple way and respond intelligently. ”
Nicholas Winsinger, Full Professor in the Department of Organic Chemistry, Faculty of Chemistry and Biochemistry, Faculty of Science, UNIGE, and last author of this study
Like “computer”
Just as computers are built on the simple logical operations of “and,” “or,” and “not,” this technology applies the same principles at the molecular level. In this first demonstration, an “and” logic gate ensures activation only in the presence of two cancer biomarkers, increasing drug selectivity.
Looking to the future, future systems may integrate additional logical operations to create medicines that behave like programmable systems and can make complex decisions within the body. This opens the door to truly “smart” medicines that adapt to the environment and tailor treatment to each patient’s unique physiology while minimizing side effects. These innovations do not replace human surveillance, but aim to make treatments more targeted and effective, bring new hope to personalized care, and transform the way we fight disease.
This research was supported by the Swiss National Science Foundation and builds on the basic research of the previous NCCR Chemical Biology Program.
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Reference magazines:
Chen, S.-K. and others. (2026). DNA-drug conjugates enable logic-gated drug delivery amplified by hybridization chain reaction. nature biotechnology. DOI: 10.1038/s41587-026-03044-0. https://www.nature.com/articles/s41587-026-03044-0
