In a lab in Prague, Dr. Marek Ondruš held up a vial containing a synthetic strand of DNA that could one day replace months of antibody development in a matter of days. At the Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences (IOCB Prague), Ondruš and his colleague Prof. Michal Hocek have cracked a long-standing bottleneck in medical diagnostics: the slow, laborious process of creating molecules that can precisely target proteins in the body. Their breakthrough centers on chemically modified DNA aptamers—short, lab-made nucleic acid sequences that bind to specific targets like antibodies do, but with far greater speed, stability, and flexibility.
Aptamers have long been seen as promising alternatives to antibodies, especially in diagnostics and targeted therapies. They don’t require living cells to produce, can be stored at room temperature, and resist harsh conditions that would degrade proteins. Yet their development has traditionally taken months, involving multiple rounds of selection to isolate the rare DNA sequence that binds tightly to a target. The Prague team’s new method slashes that timeline dramatically. By screening for entire 'aptamer families'—groups of hundreds of related sequences—they can identify high-performing candidates in just days. As Ondruš puts it, “Our new approach first screens for 'aptamer families'—hundreds of related sequences—and then identifies the best-performing member of the family. This approach can reduce development time from several months to only a few days.”
The innovation doesn’t stop at speed. The researchers chemically modified the DNA building blocks, incorporating functional groups similar to those found in amino acids—the very components that give proteins their diverse shapes and functions. This allows the aptamers to mimic protein-like interactions, vastly expanding their ability to bind complex biological targets. In a landmark demonstration, the team developed an aptamer that binds specifically to the human insulin receptor, a critical protein in blood sugar regulation. Using cryo-electron microscopy, they revealed how the chemical modifications not only enhance binding but also stabilize the aptamer’s structure—a dual advantage previously unseen in nucleic acid engineering.
Published in Nature Communications, this work opens doors to faster, more adaptable diagnostic tools and potential therapeutics. The team is now working with IOCB Tech, the institute’s technology transfer arm, to bring these aptamers into real-world applications. With demand growing for rapid, reliable detection methods—from infectious diseases to chronic conditions—this technology could redefine how we design molecular tools. As synthetic biology advances, the line between DNA and protein-like function blurs, and Prague has just taken a bold step into that future.