Interactomics and personalized pharmacotherapy – present and looking to the future

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The review highlights the advances in natural science that form the basis of the concept of personalized and precision medicine (PPM). The provisions of PPM (prediction, prevention, personalization) have been disclosed and modern molecular genetic tools have been shown, which are used in leading scientific and practical biomedical centers to improve the quality of treatment of patients with multifactorial diseases (MFD). The main principles of molecular genetic biomarking of MFDs, as well as gene technologies (CRISPR, non-coding RNA, etc.) used in medical practice and at the stage of clinical trials were highlighted. Particular attention has been paid to molecular genetic methods of targeted therapy for cancer, including antitumor vaccines. Scientific developments in the field of prediction and preventive treatment of MFD have been considered - precision healing technologies of tomorrow. The main provisions of interactomics as an interdisciplinary field of natural science have been highlighted, as well as the applied aspects of this section of fundamental science for the development of diagnostic and treatment-and-prophylactic technologies of a new generation.

作者简介

Alexander Tyukavin

Saint Petersburg State Chemical and Pharmaceutical University of the Ministry of Health of the Russian Federation

编辑信件的主要联系方式.
Email: alexander.tukavin@pharminnotech.com
SPIN 代码: 8476-5366
Scopus 作者 ID: 6603645369
Researcher ID: V-6699-2017

Doctor of Medicine (MD), Professor, Head of the Department to Physiology and Pathology

俄罗斯联邦, Saint Petersburg

Maria Studneva

Moscow State University of Food Production; EPMA (European Association for Predictive, Preventive and Personalized Medicine)

Email: maria.studneva@gmail.com

assistant of the Department to Personalized Medicine, Precision Nutrition and Biodesign

俄罗斯联邦, Moscow; Brussels

Sergei Suchkov

Moscow State University of Food Production; A.I. Yevdokimov Moscow State University of Medicine and Dentistry; EPMA (European Association for Predictive, Preventive and Personalized Medicine)

Email: ssuchkov57@gmail.com

Doctor of Medicine (MD), Professor, Head of the Department to Personalized Medicine, Precision Nutrition and Biodesign, Professor of the Department of Clinical Allergology and Immunology

俄罗斯联邦, Moscow; Moscow; Brussels

参考

  1. Suchkov S. V., ed. Basics of Personalized and Precision Medicine. Textbook for students of medical universities and faculties. Kazan: MedDoc Mublishing House; 2021. 628 p. (In Russ.).
  2. Tykavin A. I., ed. Pathology: textbook. Moscow: INFRA-M; 2021. 844 p. (In Russ.).
  3. Filatova A. Yu., Sparber P. A., Krovisheeva I. A., et al. Long noncoding RNAs are a promising therapeutic target in various diseases. Vestnik RGMU = Bulletin of RSMU. 2017:(3);5-17. https://doi.org/10.24075/BRSMU.2017-03-01. (In Russ.).
  4. Tyukavin A. I., Belostotskaya G. B., Zakharov Е. А., et al. Apoptotic Bodies of Cardiomyocytes and Fibroblasts – Regulators of Directed Differentiation of Heart Stem Cells. Bull Exp Biol Med. 2020;170(1):112-117. https://doi.org/10.1007/s10517-020-05015-0. (In Russ.).
  5. Tsarev I. L., Melerzanov A. V. Review of approaches to immunotherapy in oncology. Issledovaniya i praktika v medicine = Research and Practical Medicine Journal. 2017;4(3):51-65. https://doi.org/10.17709/2409-2231-2017-4-3-5. (In Russ.).
  6. Goryaev A. A., Savkina M. V., Obukhov Yu. I., et al. DNA and RNA Vaccines: Current Status, Quality Requirements and Specific Aspects of Preclinical Studies. BIOpreparaty. Profilaktika, diagnostika, lechenie = BIOpreparations. Prevention, Diagnosis, Treatment. 2019;19(2):72-80. https://doi.org/10.30895/2221-996X-2019-19-2-72-80. (In Russ.).

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2. Fig. 1. Latent period of disease development as a complex target of PPM

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3. Fig. 2. Viral vectors for gene therapy: A) Аdeno-associated viral vectors used for gene therapy in vivo; B) Lentiviral vectors used for ex vivo gene therapy

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4. Fig. 3. Treatment regimen of a patient with adrenoleukodystrophy with hematopoietic stem cells (HSC) transfected with a vector with a normal ABCD1 gene

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5. Fig. 4. CRISPR system: tracrRNA – trans-activating (guide) RNA; crRNA – trans-acting RNA that binds to DNA

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6. Fig. 5. Gene therapy approaches aimed at long non-coding RNAs (lncRNAs): (A) – repression of transcription using the CRISPRi mechanism; (B) – RNA interference; (C) – antisense oligonucleotides (ASO) activate RNase H – dependent degradation of the target RNA through the formation of an RNA – DNA duplex; (D) – ASO interfere with the binding of lncRNA to the repression protein complex PRC2

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7. Fig. 6. The mechanism of action of the drug «Glivec». CML Enzymeis an enzyme that stimulates tumor transformation of bone marrow cells

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8. Fig. 7. Scheme of obtaining monoclonal antibodies by the hybridoma method

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9. Fig. 8. The molecule «Herceptin» is a humanized (humanized) antibody (middle): 95% human (right) and 5% murine (left)

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10. Fig. 9. The mechanism of action of bispecific antibodies when hunting for a cell with a mutant p53 protein

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11. Fig. 10. Scheme of CAR-T cells. CAR - chimeric antigenic receptor for certain tumor cells, which is a recombinant protein consisting of 4 or more domains

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12. Fig. 11. Computed tomography one week before the injection of lymphocytes (left) and 22 months after it (right); arrows indicate degraded tumors

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13. Fig. 12. Interactomes of healthy cells

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14. Fig. 13. The gene-regulatory network reflecting the interaction of proteins with DNA

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15. Fig. 14. Schematic representation of modules of three diseases: multiple sclerosis (red), rheumatoid arthritis (yellow) and peroxisomal diseases (blue)

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16. Fig. 15. Interactome the cell of a patient with schizophrenia

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版权所有 © Tyukavin A.I., Studneva M. ., Suchkov S.V., 2021

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此作品已接受知识共享署名-非商业性使用-禁止演绎 4.0国际许可协议的许可。
 


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