Russian biochips for medicine and pharmacology
Deputy Sergey Kolesnikov suggests using domestic developments for genomic registration
Lev Feinberg, " <url>"
Deputy Chairman of the Duma Committee on Health Protection, Academician of the Russian Academy of Medical Sciences Sergey Kolesnikov (United Russia) held an international expert meeting on October 7, 2008 "Results of participation of Russian scientists in international scientific and technical cooperation on problems of medicine and pharmacology".
The meeting was organized by the United Russia Party and faction, the Parliamentary Center "High-Tech Technologies, Intellectual Property", the International Scientific and Technical Center (ISTC).
The meeting participants noted the high scientific potential of Russia in the field of biomedical and pharmacological research and the availability of highly qualified personnel, which makes it promising to expand the participation of leading Russian organizations in joint international projects, including with the involvement of funds and organizational potential of ISTC.
In the recommendation part of the final document of the meeting, it is proposed that when planning the activities of the ISTC, special attention should be paid to supporting works that contribute to the expansion of international cooperation of Russia in the field of healthcare and related socially important industries. It is recommended to strengthen the innovative orientation of the work carried out with the involvement of ISTC funds, to promote the introduction of R&D results into the Russian economy and the commercialization of the results of scientific and technical activities, including on the world market.
During the discussion, Academician S. Kolesnikov noted the work of the V. A. Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences. He recalled that currently the State Duma is discussing a bill on genetic certification, this is also one of the areas of application of the institute's developments.
Deputy Director of the Institute of Molecular Biology Alexander Sessatelev in his speech said that science is done by the hands of the young. According to him, the nanotechnology of biochips developed and implemented by the Institute makes it possible to identify, in particular, tuberculosis and its drug-resistant forms (49 mutations) within a few hours. The TB-Biochip test system allows detecting at least 95% of rifampicin- and over 80% of isoniazid-resistant strains of the causative agent of tuberculosis in less than a day. The test system is designed to determine the exact type of mutation that leads to the resistance of the causative agent of tuberculosis to rifampicin or isoniazid. At the cost of a one-day hospital stay of 800 rubles, the economic effect of using biochips per patient with a stable form of TB exceeds 25 thousand rubles.
The procedure for analysis using the LC-BIOCHIP test system includes: obtaining leukocytes from the bone marrow or blood of the patient; isolation of RNA from leukocytes; reverse transcription and two rounds of multiplex polymerase chain reaction (PCR) - amplification of cDNA fragments necessary for analysis, determining the presence of translocation; hybridization – interaction of fluorescently labeled products PCR with probes on a biochip; analysis of the fluorescent glow of the biochip cells using the Chipdedector device and the ImageWare program. The method allows to determine 1 cancer cell among 1000 normal ones. Currently, the LC-BIOCHIP test system is used in the Russian Children's Clinical Hospital (Moscow), the Morozov Children's Clinical Hospital (Moscow), the Moscow Regional Oncological Dispensary (Balashikha), as well as in the departments of hematology and oncohematology of children's clinics in the cities of Nizhny Novgorod, Novokuznetsk, Tula, Sochi, Kursk, Rostov-on-Don, Syktyvkar, Irkutsk, Voronezh, Kirov, Chita, Ryazan, Ufa, etc.
The assessor also reported on the recognition system of 30 subtypes of influenza A, including the so-called "bird flu" with H5N1 antigens. In this case, the envelope proteins of the viral particle are determined by the genes that encode them. The work is carried out jointly with the Institute of Virology named after D. I. Ivanovsky, because the Institute of Molecular Biology does not work with infections.
Chips have been created for the analysis of HIV, hepatitis B and C, herpes simplex, neonatal infections. In particular, the biochip makes it possible to identify 36 subtypes of hepatitis C. Biochips have been created to identify particularly dangerous infections (plague, anthrax, smallpox), as well as chromosomal disorders in oncological diseases. For this purpose, the test system "LC-BIOCHIP", developed at the Institute of Molecular Biology, is used to detect the most significant translocations in the genome of blast cells that lead to the occurrence of acute and chronic leukemia in children. "LC-BIOCHIP" is available in two versions: "LC-BIOCHIP" for the analysis of 8 translocations and "LC-BIOCHIP-2" for the analysis of 13 translocations. The LC-BIOCHIP-2 test system determines the following 13 chromosomal translocations: t(15;17), t(4;11), t(12;21), t(1;19), t(9;22)p190, t(9;22)p210, t(8;21), inv16, t(6;11), t(9;11), t(11;19)ENL, t(11;19)ELL, t(10;11). Molecular diagnostics allows you to choose the most appropriate treatment strategy, as well as to monitor the course of the disease and the presence of minimal residual disease after therapy, as well as genetic predisposition to cancer and individual tolerance of certain types of drugs.
The "PF-BIOCHIP" test system is used to identify and diagnose genetic predisposition to the development of oncological diseases of various etiologies and to determine individual sensitivity to certain drugs (5-fluorouracil, methotrexate, omeprazole, etc.). The "pharmacogenetic" biochip (PF-BIOCHIP), developed in 2004, is the basic molecular-a diagnostic platform for studying genetic predisposition to certain oncological diseases, as well as for determining individual sensitivity to a number of medications. Depending on the specific research or diagnostic task (for example, depending on the form of the disease being studied), the biochip can be easily modified. With the help of the developed biochip for the genes of the biotransformation system, it is possible not only to analyze the genetic predisposition to lung cancer, leukemia, lymphoma, epilepsy, endometriosis, psoriasis and many other diseases, but also to use the results obtained with its help to correct the dose of drugs, as well as to use it when creating a "genetic passport". The sensitivity of the method is 10 ng, that is, at least 10 ng of genomic DNA must be added to the reaction at the first stage. PF-BIOCHIP was tested on 25 control and more than 1100 diagnostic samples. In the control samples, mutations were determined earlier using two other methods: PDRF analysis and sequencing. Comparison of restriction analysis, sequencing and hybridization data on a microchip showed a complete coincidence of the results.
The most important area of work of the Institute of Molecular Biology is the development of genetic markers of personality. For this purpose, the IL-Biochip test system is designed, which allows analyzing the polymorphism of three HLA genes-DQA1, AB0, AMEL. The method makes it possible to characterize each person genetically by a set of single-nucleotide substitutions at these loci, as well as to obtain phenotypic information about the individual's blood group and gender. The IL-BIOCHIP test system can be recommended for use at the initial stage of forensic genetic examinations. Currently, the main methods used in forensic medical practice are serological blood analysis and molecular genetic analysis of polymorphic genome loci known as tandem repeats with varying number of copies (STR-analysis). However, serological blood analysis is often difficult in cases of degraded samples and is not informative enough, because it divides the entire population into only 4 groups. STR analysis provides a high probability of identification, but is a rather complex and expensive method. The analysis using the IL-Biochip test system is more accurate and informative compared to serological. At the same time, it is much less time-consuming, material and human resources than STR-analysis and therefore can be recommended at the preliminary stages of genetic examination. The amount of DNA contained in about 100 human cells is sufficient for the analysis. This amount of DNA can be obtained, for example, from traces of saliva on a cigarette butt or on the wall of a glass from which a person drank. The IL-Biochip test system divides the entire population into 1,350. The probability that this genotype belongs to a specific person, and is not the result of a random coincidence is 99.6%.
Biological microchips allow for quantitative immunoanalysis: diagnosis of prostate cancer. OM-BIOCHIP test system (PSA); determination of six cancer markers (AFP, HCG, REA, NSE, two forms of PSA).
The representative of the Institute of Molecular Biology explained that genetic polymorphism determines hereditary predisposition to many multifactorial diseases, including cancer, and also underlies individual sensitivity to drugs. Identification of associations of polymorphic alleles of genes with a specific disease and response to drug therapy allows not only to identify the mechanisms of the disease and investigate its nature, but also to develop approaches to "personalized" medicine, i.e. treatment that takes into account the biochemical individuality of each patient. In addition, due to the variability of allele frequencies in different populations, the identification of the relationship of gene polymorphism with the risk of developing cancer, as well as with the effectiveness of treatment of these diseases is relevant for each population group.
Portal "Eternal youth" www.vechnayamolodost.ru08.10.2008