Abstract: In recent years, the free-living flatworm Macrostomum lignano has been added to the list of model organisms, which has proven itself applicable in a number of research areas. Its key feature – a high potential for regeneration – provides it with resistance to toxic compounds and oncogenes, high adaptability to sudden changes in environmental factors, as well as a long life span bordering on conditional immortality. On the other hand, the peculiarities of the chromosomal composition of the M. lignano genome, expressed in a number of genomic instabilities, coupled with regeneration that does not turn into tumor genesis, opens up wide opportunities for fundamental research of anti-cancer therapies. This review is devoted to the analysis of the areas of biological sciences where M. lignano is used or could be used.
Key words: regeneration; neurogenesis; polyploidy; genome instability; aging; flatworms; Macrostomum.
For citation: Dmitrieva A.M., Chepurnov G.Yu., Plotnikov K.O., Blinov A.G., Biryukov M.Yu. Macrostomum lignano as a model object for modern researches. Pisma v Vavilovskii Zhurnal Genetiki i Selektsii = Letters to Vavilov Journal of Genetics and Breeding. 2024;10(4):187-198. DOI 10.18699/letvjgb-2024-10-22 (in Russian)
Funding: The study was carried out with the financial support of the state budget project FWNR-2022-0016.

Abstract: A mathematical segregation model based on the fundamental properties of the normal distribution is described. A classification of segregations and their correlation with a research methodology oriented towards the predominant use of quantitative (measured) traits is proposed. An algorithm for sequential division of bi- and multimodal samples into separate groups is described, which uses the symmetry property of the normal distribution. A method for balancing groups is proposed, which improves the accuracy of dividing the original sample and unifies the calculation of the number of objects in groups. The applicability of the described method to complex distributions of various types is demonstrated, which ensures the determination of the segregation formula for the identified groups. Information is provided on access to the executable module and source codes of a specially developed tool.
Key words: genetics of quantitative traits; splitting; mathematical model; normal distribution; statistics; non-Mendelian inheritance.
For citation: Rechkin D.V. Analysis of quantitative traits segregation based on fundamental properties of the normal distribution. Pisma v Vavilovskii Zhurnal Genetiki i Selektsii = Letters to Vavilov Journal of Genetics and Breeding. 2024;10(4):199-203. DOI 10.18699/ letvjgb-2024-10-25 (in Russian)

Abstract: Adeno-associated viruses (AAVs) have become an integral part of scientific research in fields ranging from molecular biology to physiology. AAV has had a remarkable evolution from being a virus in 1965 to being a stable molecular biology tool today. Researchers are attracted to their reliability, stable transgene expression and low immunogenicity. In many cases, AAV can be an attractive delivery vehicle for gene therapy. Clinical trials using AAV as a gene therapy delivery system are being initiated by an increasing number of pharmaceutical companies. FDA approves Roctavian for AAV-based treatment of hemophilia A in 2023. This progress in the field has led us to think about its conceptual generalization and the writing of this literature review. This article reviews the latest molecular biological and biotechnological solutions for adeno-associated virus delivery, its optimization in animal models, and ways to make it more targeted. The characteristics of the serotypes of adeno-associated viruses are described, with special attention to their tropisms to the cells of the body, and genetic engineering methods to modify them: directed evolution of capsids, use of chimeric capsids crosslinked with receptors or single-chain antibodies of alpacas. A major disadvantage of AAV is the limited size of the cassette – only 4.7 kb of genetic material. The review also describes techniques for increasing the amount of genetic material transferred and for performing transduction of cDNA sequences up to 10 kb in length. The review gathers information on ongoing clinical trials using AAV and also describes the challenges of implementing gene delivery when using AAV in therapy.
Key words: Adeno-associated viruses (AAV); viral delivery; gene therapy; capsid modification; clinical studies.
For citation: Marchenko S.A., Lanshakov D.A. Principles for using recombinant adeno-associated viruses in research and therapy. Pisma v Vavilovskii Zhurnal Genetiki i Selektsii = Letters to Vavilov Journal of Genetics and Breeding. 2024;10(4):204-215. DOI 10.18699/ letvjgb-2024-10-24 (in Russian)
Funding: The work was carried out with the financial support of the Russian Science Foundation (project No. 24-25-00154).

Abstract: Reversible methylation of mRNA – modification of N6-methyladenosine (m6A) – affects almost all stages of its metabolism. Dynamic and reversible processes are regulated by “writing” m6A-methyltransferases, “erasing” m6A-demethylases and “reading” m6Abinding proteins. These regulators recognize, add or remove sites modified by m6A, changing biological processes accordingly. m6A is present in many mRNAs encoded by genes associated with human diseases, including cancer. The role of m6A mRNA modification in tumor formation and progression is mainly associated with activation of oncogenes expression and suppression of suppressor gene expression. At the same time, depending on the modulation of m6A levels, expression and activity of m6A enzymes and other factors, this modification of mRNA can lead to both activation and inhibition of tumor growth. Great importance is attached to the participation of m6A in the regulation of tumor angiogenesis, as well as its progression, in the relationship between m6A and other epigenetic modifications, a violation of the regulation of which can cause oncogenesis. The underlying molecular mechanism of METTL3 is a possible target for the treatment and diagnosis of human diseases, which, according to results, could be useful in the diagnostics and treatment of malignancies. This is evidenced by the effect on tumor growth of METTL3 and angiogenesis inhibitors, which have shown efficacy in some types of cancer.
Key words: m6A mRNA; oncogenesis; tumor microenvironment; angiogenesis; transposons; relationship of m6A with chromatin.
For citation: Nikolin V.P., Popova N.A., Rykova E.Y. The role of m6A mRNA methylation in the pathogenesis of a malignant tumor. Pisma v Vavilovskii Zhurnal Genetiki i Selektsii = Letters to Vavilov Journal of Genetics and Breeding. 2024;10(4):216-223. DOI 10.18699/ letvjgb-2024-10-25 (in Russian)
Funding: This work was supported by State Budgetary Project FWNR-2022-0016.

Abstract: Genome editing is a promising method for improving agronomic valuable traits in bread wheat (Triticum aestivum L.), with the bioballistic method being one of the most common techniques for delivering genetic constructs. Most published studies on editing bread wheat have used a few model varieties. However, transformation efficiency has been shown to be genotype-dependent, making it essential to optimize conditions for successful transformation of non-model genotypes. In this study, we compared the effectiveness of bioballistics for transforming immature scutellum of the common wheat line Velut using various parameters: the type and concentration of microcarriers (20, 40 mg/ml for gold microparticles and 50 mg/ml for tungsten) and helium pressure (650 and 1100 psi). Transformation efficiency was evaluated by the average number of eGFP-expressing cells per explant. It was concluded from the results obtained that transformation efficiency decreased when using tungsten particles at both 650 psi and 1100 psi, as well as gold particles at 1100 psi and 40 mg/mL, due to increased scutellum damage. This study demonstrated that the highest transformation efficiency was achieved using gold microcarriers with the following parameter combinations: a particle concentration of 20 mg/ml at 1100 psi, or 40 mg/ml at 650 psi.
Key words: transformation; bioballistic; wheat; line Velut; immature scutellum.
For citation: Nesterov M.A., Kiseleva A.A., Timonova E.M., Sergeeva E.M., Salina E.A. Optimization of bioballistic parameters for transformation of common wheat Triticum aestivum L. line Velut. Pisma v Vavilovskii Zhurnal Genetiki i Selektsii = Letters to Vavilov Journal of Genetics and Breeding. 2024;10(4):224-230. DOI 10.18699/letvjgb-2024-10-26 (in Russian)
Funding: Исследование выполнено за счет бюджетных средств FWNR-2024-0009.