Scientists from the Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic have developed a breakthrough technology for the efficient development of aptamers. The new method connects several biochemical and bioinformatics steps and paves the way for new diagnostic and therapeutic applications. These include, for example, wearable sensors capable of monitoring the levels of selected biomarkers in the body in real time and providing timely warning of impending health complications.
The results were published in the journal 《Nature Communications》 .
Aptamers are short chains of DNA or RNA that can very precisely recognize and bind to a specific target molecule. Similar to antibodies, they can be used to detect or influence the function of these molecules. However, unlike antibodies, they are much more stable, can be produced synthetically, and can be precisely chemically modified according to the desired properties. This allows them to acquire properties that cannot be achieved with antibodies.
With the growing demand for accurate and rapid diagnostic tools, aptamers are in many cases more suitable than antibodies alone. However, their development process is experimentally and time-consuming and requires experts from several scientific disciplines. A team of scientists from the Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic (IOCB) led by Marek Ondruš and Michal Hock has now developed a technology that significantly shortens the entire development process.
"Aptamer development often resembles searching for a needle in a haystack. In a mixture of trillions of different DNA sequences, we try to find the only one that binds strongly and specifically to the target molecule. Our new approach allows us to first find 'aptamer families' - hundreds of sequences with a certain similarity and then identify the family member that shows the best experimental properties. This element contributes to shortening the development from several months to days," says Marek Ondruš.
Researchers have also expanded the possibilities of using aptamers . Their building blocks are chemically modified - they attach new functional groups to them, which can be found naturally, for example, in amino acids. The molecules created in this way combine the advantages of both DNA and antibodies: the order of the individual building blocks is determined by the order of the letters in DNA, and thanks to the variety of attached chemical modifications, the aptamer's ability to recognize biologically important targets and mimic interactions typical of proteins, which are the basis of many biological processes, is significantly expanded.
The researchers demonstrated the potential of the new method on the human insulin receptor , a key protein involved in blood sugar regulation. They developed an aptamer that specifically binds to the receptor and used cryo-electron microscopy to describe the molecular mechanism of mutual binding in detail.
"We have shown that chemically introduced functional groups are of fundamental importance not only for the recognition and formation of the aptamer complex with the protein, but also for the stabilization of the DNA aptamer structure itself. Our results provide a new insight into how the properties of proteins can be mimicked using chemically modified nucleic acids," summarizes Marek Ondruš.
The technology could complement or even replace antibody-based diagnostic tools in the future . The researchers are collaborating on further developing the technology with IOCB Tech , a company that helps translate discoveries from the IOCB into practice.
