17 November 2022

Aptamers for diagnostics

Siberian scientists create new test systems based on aptamers

Kirill Sergeevich, "Science in Siberia"

Scientists from the Institute of Chemical Biology and Fundamental Medicine SB RAS together with the staff of the Research Institute of Clinical and Experimental Lymphology — branch of the Institute of Cytology and Genetics SB RAS are developing new test systems based on aptamers for the diagnosis and monitoring of Bekhterev's disease. The implementation of this idea will make it possible to detect the disease at an early stage and prevent a decrease in the quality of life of patients.

Ankylosing spondylitis, or Bekhterev's disease, is an autoimmune inflammatory rheumatic disease that develops in people under the age of 40 and is characterized by damage to the sacroiliac joints and spine, which can lead to disability and disability. The patient has pain and stiffness in the back, lower back, as well as limited mobility. According to statistics, in the Novosibirsk region, 3 cases of ankylosing spondylitis are diagnosed per 10,000 inhabitants. The number of detected cases of the disease is lower than the same indicator in the world and is due to the fact that the existing diagnosis does not allow to reliably determine the disease in the early stages. According to scientists, in the vast majority of patients, the exact diagnosis is confirmed for the first time only seven years after the first clinical manifestations of the disease. Such a long period leads to the fact that the need for expensive therapy becomes much higher than in other immuno-inflammatory rheumatic diseases. 

"The activity of the disease can be detected by the level of certain biomarker proteins in the blood serum, for which test systems are being developed. Now, as a rule, all over the world, enzyme immunoassay based on specific antibodies is used to determine these biomarkers. The method is quite accurate, but it has its limitations. Antibodies are protein—based molecules that are obtained in a biotechnological way. For the study of diseases that have been going on for years, antibody-based test systems give insufficient reproducibility — the results of the first and repeated analyses may differ. In addition, antibodies are sensitive to storage and transportation conditions. Therefore, it is important to develop new test systems in which the elements reacting to the analyzed compound in the blood serum will be represented not by antibodies, but by some alternative molecules," says project manager, Head of the Laboratory of RNA Chemistry of the IHBFM SB RAS Candidate of Chemical Sciences Maria Alexandrovna Vorobyeva. 

Aptamers.jpg

Scheme of colorimetric analysis using a test system based on aptamers

Scientists suggest that new aptamer-based test systems should solve the problem of timely detection of Bekhterev's disease in the early stages and improve the effectiveness of treatment. Aptamers are molecules that are obtained artificially by chemical synthesis in the laboratory. The peculiarity of aptamers is that they are able to form a complex structure with a known sequence of nucleotides and identify specific target proteins showing the activity of the disease. 

"An aptamer is a molecule of a strictly defined composition that can be made in any laboratory where there is an oligonucleotide synthesizer, because its nucleotide sequence is always known and stored digitally. Aptamers are not inferior to antibodies in their ability to analyze biomarkers, and in some cases even surpass them. The main advantages of aptamers are that they have high stability, are less demanding on storage conditions, and since they are synthesized chemically, they can be further modified," emphasizes M. A. Vorobyova. 

Such test systems are often based on the principle of colorimetry - changing the color of the solution in the presence of the analyzed compound. The more intense the color, the more substance in the blood. Also, according to scientists, it is important that the new test system is simple and compatible with the equipment of clinical diagnostic laboratories, adapted to the usual methods of analysis. 

"The problem of early diagnosis is very relevant for ankylosing spondylitis. Currently, there are no reliable tests for blood biomarkers that would allow accurate diagnosis of the onset of the disease. From the moment of the onset of the disease and a reliable diagnosis, about 8-10 years pass, and the time for the most effective treatment has already been missed. Detection of the disease at the initial stages will greatly facilitate the life of both patients and doctors. For this reason, colleagues, clinical rheumatologists, became interested in our developments, and we began to work together," says the researcher. 

In the future, according to scientists, aptamer-based test systems can become universal. In the presence of data on specific specific biomarkers, such test systems can be used to detect not only inflammatory, but also cardiovascular, infectious and oncological diseases. 

The research is carried out with the support of the Russian Science Foundation and the Government of the Novosibirsk Region (project No. 22-15-20050).

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