How can doctors destroy cancer cells without damaging healthy tissue? This question remains one of the biggest challenges in modern oncology. Researchers at the University of Geneva (UNIGE) have developed a “smart” system built from synthetic DNA strands that can identify cancer cells with remarkable precision and release powerful drugs only where they are needed. This approach points to the future of programmable and responsive medicines in addition to cancer treatment. Here are the findings: nature biotechnology.
Targeted therapies are already reshaping cancer treatment by delivering drugs directly to tumors, reducing damage to healthy cells and helping to alleviate the harsh side effects associated with chemotherapy. One of the most successful strategies is antibody-drug conjugates (ADCs), which use monoclonal antibodies to deliver therapy directly to cancer cells.
However, ADCs still have drawbacks. Their relatively large size may limit their penetration into the tumor, allowing them to carry only a limited amount of drug. These challenges have led scientists to seek new ways to more effectively deliver treatments.
DNA-based drug delivery offers new benefits
To overcome these limitations, the UNIGE team designed a system based on short DNA strands. These molecules are much smaller than antibodies, so they can pass through tumor tissue more easily. They can also be designed to carry multiple components to increase their potential effectiveness.
“Two-key” system for precise drug activation
The new method relies on several separate DNA strands, each responsible for a specific function. Some chains contain binding agents that recognize cancer markers, while others contain toxic drugs.
When two different cancer markers are present on a cell, DNA components attach to them and cluster in precise locations. This sets off a chain reaction that builds more DNA structures at that site, increasing the amount of drug delivered. This process is very similar to two-factor authentication on banking websites. Both markers must be detected before activation can occur. If any one is missing, the reaction will not be initiated and the drug will remain inactive.
Laboratory results show high selectivity and power
In laboratory experiments, the system was able to identify cancer cells with specific combinations of surface proteins and deliver potent drugs directly to the cells. Nearby healthy cells were unaffected.
The researchers also showed that multiple drugs can be delivered together using this approach. This could be important for preventing or overcoming resistance, a common problem in cancer treatment.
“This could represent an important step in the evolution of medicine with the introduction of self-manipulating drug systems. Until now, computers and AI have helped in the design of new drugs. What is new here is that the drugs themselves can ‘compute’ biological signals in a simple way and respond intelligently,” explains Nicholas Winsinger, full professor in the Department of Organic Chemistry, Faculty of Chemistry and Biochemistry, Faculty of Science, UNIGE, and final author of the paper. Study.
Drugs that function like “computers”
This system works using the same kind of basic logic as computing. Just as computers rely on operations such as “and,” “or,” and “not,” this technology applies similar rules at the molecular level. In this case, the “and” logic gate ensures that the drug is activated only when both cancer markers are present, increasing treatment selectivity.
Aiming for programmable “smart” medicine
In the future, the researchers hope to extend this concept by adding more complex logical functions. This could lead to the development of drugs that behave like programmable systems and can make more sophisticated decisions within the body.
Such treatments have the potential to adapt to each patient’s unique biology and improve efficacy while reducing side effects. Rather than replace doctors, these systems are designed to increase precision and control of treatment, open new possibilities for personalized medicine, and reshape the way we treat diseases.
The research was supported by the Swiss National Science Foundation and builds on earlier work from the NCCR Chemical Biology Program.
