Scientists create “smart” DNA drug that targets cancer cells with extreme precision
Université de Genève
Targeted therapies have already reshaped cancer care by
directing drugs straight to tumors, helping reduce damage to healthy cells and
easing harsh side effects linked to chemotherapy. One of the most successful
strategies involves antibody-drug conjugates (ADCs), which use monoclonal
antibodies to carry treatments directly to cancer cells.
However, ADCs still have drawbacks. Their relatively large
size can limit how well they penetrate tumors, and they can only carry a
limited amount of drug. These challenges have pushed scientists to explore new
ways to deliver therapies more effectively.
DNA-Based Drug Delivery Offers New Advantages
To overcome these limitations, the UNIGE team designed a
system based on short DNA strands. Because these molecules are much smaller
than antibodies, they can move more easily through tumor tissue. They can also
be engineered to carry multiple components, increasing their potential
effectiveness.
A "Two-Key" System for Precision Drug
Activation
The new method relies on several separate DNA strands, each
carrying a specific function. Some strands include binders that recognize
cancer markers, while another carries a toxic drug.
When two distinct cancer markers are present on a cell, the
DNA components attach to them and assemble at that exact location. This
triggers a chain reaction that builds up more DNA structures at the site,
boosting the amount of drug delivered. The process works much like two-factor
authentication on a banking website. Both markers must be detected before
activation occurs. If one is missing, the reaction does not begin, and the drug
remains inactive.
Lab Results Show High Selectivity and Power
In laboratory experiments, the system successfully
identified cancer cells with specific combinations of surface proteins and
delivered potent drugs directly to them. Nearby healthy cells were not
affected.
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 mark an important step forward in the
evolution of medicine, with the introduction of a self-operating drug system.
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," explains Nicolas Winssinger, full professor in the
Department of Organic Chemistry of the School of Chemistry and Biochemistry,
Faculty of science, UNIGE, and last author of the study.
Drugs That Act Like "Computers"
The system works using the same kind of basic logic found in
computing. Just as computers rely on operations like "and,"
"or," and "not," this technology applies similar rules at
the molecular level. In this case, an "and" logic gate ensures that
the drug activates only when both cancer markers are present, making the
treatment highly selective.
Toward Programmable "Smart" Medicines
In the future, researchers hope to expand this concept by
adding more complex logic functions. This could lead to medicines that behave
like programmable systems, capable of making more advanced decisions inside the
body.
Such treatments could adapt to each patient's unique
biology, improving effectiveness while reducing side effects. Rather than
replacing doctors, these systems are designed to enhance precision and control
in therapy, opening new possibilities for personalized medicine and reshaping
how diseases are treated.
The research was supported by the Swiss National Science
Foundation and builds on earlier work from the NCCR Chemical Biology program.
Journal Reference:
- Si-Kai
Chen, Miguel López-Tena, Francesco Russo, Emma E. Watson, Millicent
Dockerill, Javier Cabello Garcia, Sofia Barluenga, Nicolas
Winssinger. DNA–drug conjugates enable logic-gated drug delivery
amplified by hybridization chain reactions. Nature
Biotechnology, 2026; DOI: 10.1038/s41587-026-03044-0