Review
Pharmacology & Pharmacy
Kenji Rowel Q. Lim, Toshifumi Yokota
Summary: FSHD is a genetic disorder characterized by progressive muscle weakness, affecting approximately 20% of patients who may become wheelchair-bound. The disease is caused by aberrant expression of the DUX4 gene, with potential treatments aiming to reduce DUX4 expression or its toxic protein activity. Genetic approaches such as oligonucleotide and genome editing technologies are being developed to target these goals.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Yu Wang, Shuting Chen, Jingyi Zhang, Qing Ye, Yin Liu
Summary: DNA nanomaterials, as a novel type of nanomaterials, have great potential in biomedical applications due to their high precision, controllability, and biocompatibility. Therapeutic drugs based on DNA nanomaterials have shown beneficial effects on various diseases. However, the instability of DNA nanomaterials greatly hinders their clinical application. In this study, we designed and synthesized a stable topological DNA nanostructure, DNA Nano Trihedron (DNT), which could enter MCF-7 cells without a transfection agent. DNT induced significant changes in gene expression and exhibited significant inhibitory effects on MCF-7 cells. Even after two months of storage, DNT still retained its inhibitory effect on MCF-7 cells.
Article
Chemistry, Multidisciplinary
Jinpeng Han, Yuchen Cui, Feng Li, Zi Gu, Dayong Yang
Summary: This study utilized natural polyphenol tannic acid (TA) to control the assembly and disassembly of nucleic acid nanocomplexes in cells for smart drug delivery and gene therapy. Through strong affinity between TA and nucleic acids/membrane proteins, the nanocomplex effectively targets cells and achieves spatiotemporally controllable disassembly within cells.
Article
Chemistry, Multidisciplinary
Kim Nguyen, Yajun Wang, Whitney E. England, John C. Chaput, Robert C. Spitale
Summary: The study demonstrates the utility of XNAzyme X10-23 in targeting allele-specific mRNA sequences in cells, particularly for difficult-to-treat disease-causing mutations. Catalytic XNAs show potential for suppressing mRNA expression carrying disease-causing mutations that are challenging to target at the protein level with conventional small molecule therapeutics.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Analytical
Stilianos G. Roussis, Isaiah Cedillo, Claus Rentel
Summary: Substitution of an oxygen atom with sulfur in the phosphate diester linkage of oligonucleotide leads to increased nuclease resistance and enhanced protein binding, while also resulting in complex mixtures of diastereoisomers. Chromatographic separation of diastereoisomers in oligonucleotides with phosphorothioate diester linkages is currently limited to those with only four or five PS linkages.
ANALYTICAL CHEMISTRY
(2021)
Review
Pharmacology & Pharmacy
Kenneth A. Myers, Ingrid E. Scheffer
Summary: Epilepsy is a genetically heterogeneous condition, with genetic factors playing a role in most patients. Over 50% of patients with infantile-onset developmental and epileptic encephalopathy (DEE) now have a genetic diagnosis. Precision medicine approaches have the potential to significantly improve the quality of life for these children and their families.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY
(2022)
Editorial Material
Genetics & Heredity
Muhammad Riaz Khan, Raymund J. Wellinger, Benoit Laurent
Summary: Long noncoding RNA (lncRNA) genes, like protein-coding genes, consist of introns and exons and undergo constitutive and/or alternative splicing after transcription. This review outlines the current understanding of lncRNA splice variants and their functional implications in cell biology.
TRENDS IN GENETICS
(2021)
Review
Clinical Neurology
Jean-Baptiste Brunet De Courssou, Alexandra Durr, David Adams, Jean-Christophe Corvol, Louise-Laure Mariani
Summary: Advances in targeted regulation of gene expression have opened up new therapeutic approaches for monogenic neurological diseases, with antisense therapies relying on modified nucleotide sequences showing promise in treating severe and previously untreatable disorders. Despite the success seen in various neurological disorders, there remain many unknowns and challenges to expanding these treatments to other diseases. Further research and development is needed to fully realize the potential of personalized medicine targeting the pathogenic roots of these conditions.
Article
Chemistry, Organic
Tamilselvan Rajasekaran, Graeme C. Freestone, Rodrigo Galindo-Murillo, Barbara Lugato, Hans Gaus, Michael T. Migawa, Eric. E. Swayze, Thomas E. Cheatham III, Punit P. Seth, Stephen Hanessian
Summary: This manuscript describes a chemical strategy to preorganize a trinucleotide subunit in a conformation suitable for base pairing, using bis-phosphonate esters bridging hydrocarbon tethers to create macrocyclic analogues. The synthesis and incorporation of eight P-stereoisomers of these analogues into oligonucleotides (ONs) is described, and their effect on hybridization kinetics with RNA is characterized. The size of the macrocyclic tether and configuration at phosphorus significantly influenced the on-rates and off-rates of the modified ONs. The results highlight the potential of backbone-constrained macrocyclic nucleic acid analogues in modulating hybridization kinetics.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Clinical Neurology
Saija Ahonen, Silvia Nitschke, Tamar R. Grossman, Holly Kordasiewicz, Peixiang Wang, Xiaochu Zhao, Dikran R. Guisso, Sahba Kasiri, Felix Nitschke, Berge A. Minassian
Summary: Lafora disease is a fatal progressive myoclonus epilepsy caused by the accumulation of long branches in glycogen molecules leading to the formation of Lafora bodies. In mouse models, targeting the GYS1 mRNA with an antisense oligonucleotide (Gys1-ASO) prevented the formation of Lafora bodies and halted disease progression, showing promise as a potential therapy for this catastrophic epilepsy.
Article
Biochemistry & Molecular Biology
Lingdi Zhang, Timothy A. Vickers, Hong Sun, Xue-hai Liang, Stanley T. Crooke
Summary: Toxic PS-ASOs can cause nucleolar mislocalization of proteins and induce conformational changes by binding to proteins like RNase H1, affecting protein-protein interactions. Stronger binding of PS-ASOs leads to more significant conformational changes and may explain the cytotoxic effects of some PS-ASOs.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Ze-Kun Wang, Jia-Le Lin, Yun-Chang Zhang, Chen-Wu Yang, Ya-Kun Zhao, Zheng-Wei Leng, Hui Wang, Dan-Wei Zhang, Jiang Zhu, Zhan-Ting Li
Summary: Five water-soluble flexible organic frameworks were synthesized by quantitatively forming a hydrazone bond in water, displaying tunable diameters and low cytotoxicity. These frameworks can quickly include and deliver DNA into cells, with a delivery rate of up to 99.5%.
MATERIALS CHEMISTRY FRONTIERS
(2021)
Article
Pharmacology & Pharmacy
Mohadeseh Dastpeyman, Ramin Sharifi, Azin Amin, John A. Karas, Brittany Cuic, Yijun Pan, Joseph A. Nicolazzo, Bradley J. Turner, Fazel Shabanpoor
Summary: This study demonstrates that integrating endosomal escape domains with CPPs can improve the intracellular delivery efficiency of ASOs, and enhance the efficiency of BBB-permeability and CNS activity of systemically administered ASOs.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Article
Chemistry, Multidisciplinary
Svetlana V. Vasilyeva, Elizaveta E. Baranovskaya, Evgeniya S. Dyudeeva, Alexander A. Lomzov, Dmitrii Pyshnyi
Summary: In this study, we synthesized new oligonucleotide derivatives with N-benzimidazole, N-benzoxazole, N-benzothiazole, and 1,3-dimethyl-N-benzimidazole phosphoramide groups. These modifications were introduced using azides during solid-phase oligonucleotide synthesis. The new modifications have bulk heterocyclic structures, similar to purine nucleoside bases. The modified oligonucleotides showed high yields and the possibility of multiple modifications, which is important for further applications.
Article
Biochemistry & Molecular Biology
Karima Relizani, Lucia Echevarria, Faouzi Zarrouki, Cecile Gastaldi, Chloe Dambrune, Philippine Aupy, Adrian Haeberli, Marek Komisarski, Thomas Tensorer, Thibaut Larcher, Fedor Svinartchouk, Cyrille Vaillend, Luis Garcia, Aurelie Goyenvalle
Summary: Tricyclo-DNA (tcDNA) is a promising oligonucleotide analog with therapeutic potential, especially when conjugated with palmitic acid for improved delivery to muscle tissues. This conjugation enhances the potency of tcDNA-ASO, resulting in functional improvement in dystrophic mice with significantly reduced dose, while also showing a promising safety profile for clinical development in neuromuscular diseases.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Tatyana P. Makalish, Ilya O. Golovkin, Volodymyr V. Oberemok, Kateryna V. Laikova, Zenure Z. Temirova, Olesya A. Serdyukova, Ilya A. Novikov, Roman A. Rosovskyi, Andrey I. Gordienko, Evgeniya Yu. Zyablitskaya, Elvina A. Gafarova, Kseniya A. Yurchenko, Iryna I. Fomochkina, Anatoly V. Kubyshkin
Summary: The study demonstrates the potential of Cytos-11 antisense oligonucleotide in treating rheumatoid arthritis by effectively suppressing TNF-alpha gene expression, reducing joint inflammation, and inhibiting pannus development, showing comparable results to adalimumab.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Editorial Material
Cell Biology
V. V. Oberemok, O. A. Andreeva, K. V. Laikova, I. A. Novikov, A. V. Kubyshkin
Summary: The coronavirus pandemic highlights the need for effective vaccines against viral diseases. New platforms for vaccine creation, such as adenovirus vectors and mRNA vaccines, have shown potential in preventing coronavirus infection. However, these platforms have the disadvantage of limited antigen presentation, allowing the virus to evade immunity. The development of new vaccine platforms that can adapt to virus subtypes is urgently needed.
INFLAMMATION RESEARCH
(2022)
Review
Cell Biology
V. V. Oberemok, O. A. Andreeva, K. V. Laikova, I. A. Novikov, Y. V. Puzanova, A. V. Kubyshkin
Summary: The worldwide vaccination rate has reached enormous proportions, with at least 75% of the world's population likely to be vaccinated. There is controversy surrounding plans to vaccinate young people under 20, despite the significantly higher mortality rate among those aged 65 and older. The question of vaccinating individuals who already have antibodies and memory cells from contracting and surviving the virus is also a thorny issue. The consequences of large-scale vaccination are difficult to predict, especially when some people have limited access to vaccines while others have already received multiple doses.
INFLAMMATION RESEARCH
(2022)
Article
Cell Biology
Maxim A. Kriventsov, Yulianna A. Yermola, Alexandra A. Davydova, Alexey A. Beketov, Tatyana P. Makalish, Evgeniya Yu Zyablitskaya, Alina Geraschenko, Anatoly Kubyshkin, Anna A. Galyshevskaya, Anastasia Zausalina
Summary: This study analyzed myocardial samples from critically ill COVID-19 patients and found minimal or no expression of vitamin D receptors (VDRs) in cardiomyocyte nuclei, while lymphoid cells still showed strong expression. These findings provide interesting insights for further research on the effects of ligand-associated VDR activation on the cardiovascular system.
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
(2022)
Article
Endocrinology & Metabolism
Iuliana I. Shramko, Elizaveta S. Ageeva, Konstantin D. Maliy, Irina N. Repinskaya, Cyrill O. Tarimov, Iryna I. Fomochkina, Anatolii V. Kubishkin, Olga V. Ostapenko, Anna K. Gurtovaya, Suman Shekhar
Summary: Abdominal obesity coupled with polygenic hereditary defects is considered the initial event in the development of metabolic syndrome (MS). This study analysed the frequency of adiponectin (ADIPOQ) and leptin (LEP) gene polymorphisms in MS patients and their association with MS symptoms. The most common variant of the ADIPOQ (rs2241766) gene among MS patients was the GT genotype, while the A allele of the LEP (rs7799039) gene was the most frequent. MS patients carrying the GG genotype of the LEP (rs7799039) gene had the highest systolic blood pressure. ADIPOQ (rs2241766) GT genotype carriers were associated with the highest systolic blood pressure and body mass index (BMI), while ADIPOQ (rs2241766) GG genotype carriers were associated with the highest diastolic blood pressure, hyperglycemia, and elevated glycated hemoglobin (HbA1c). This study identified unique gene variants associated with the risk of developing MS in the Crimean population.
JOURNAL OF DIABETES RESEARCH
(2022)
Editorial Material
Cell Biology
A. Kubyshkin, E. Kovalenko
Summary: This article summarizes the 15th World Congress on Inflammation (WCI2022), held in Rome, Italy from June 5 to 8, 2022. It presents the main trends and promising research developments in inflammation, including cellular and molecular mechanisms, new pathogenetic pathways, target molecules, genetic mechanisms, and therapeutic strategies. Additionally, it describes the primary areas of research in inflammatory pathology mechanisms engaged by leading scientific groups and national societies from various countries.
INFLAMMATION RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Volodymyr V. Oberemok, Refat Z. Useinov, Oleksii A. Skorokhod, Nikita V. Gal'chinsky, Ilya A. Novikov, Tatyana P. Makalish, Ekaterina V. Yatskova, Alexander K. Sharmagiy, Ilya O. Golovkin, Yuri I. Gninenko, Yelizaveta V. Puzanova, Oksana A. Andreeva, Edie E. Alieva, Emre Eken, Kateryna V. Laikova, Yuri V. Plugatar
Summary: Insects outnumber humans in terms of species and total biomass. The use of chemical insecticides leads to harmful effects on ecosystems and decreased insect diversity. This article introduces a natural way of regulating insect pests by using extracellular double-stranded DNA secreted by a plant. The topical application of artificially synthesized short antisense oligonucleotide insecticides is shown to be an effective and selective method of controlling Coccus hesperidum.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Mechanics
A. Kubyshkin, I. N. Belokon, V. V. Karagodin
Summary: The possibility of intercepting ballistic missiles by American sea-based antimissiles is analyzed in this study. The mathematical modeling results show that using liquid propulsion systems on the interceptor can greatly expand the interception zones. Meanwhile, the launch window is divided into two spatially separated regions, allowing for the maximization of both defensive and offensive capabilities.
MECHANICS OF SOLIDS
(2022)
Review
Entomology
Volodymyr V. Oberemok, Nikita V. Gal'chinsky, Refat Z. Useinov, Ilya A. Novikov, Yelizaveta V. Puzanova, Roman I. Filatov, Nanan J. Kouakou, Kra F. Kouame, Kouadio D. Kra, Kateryna V. Laikova
Summary: Sternorrhyncha representatives are serious pests of agriculture and forestry, causing damage to woody plants. They serve as vectors for viral diseases and release honeydew, leading to fungal diseases. Innovative and environmentally friendly insecticides are needed to control their population. This review examines distinct species from four superfamilies, highlighting their adaptations and suggesting new ways of using insecticides for plant protection.
Article
Pharmacology & Pharmacy
Volodymyr V. Oberemok, Kateryna V. Laikova, Kseniya A. Yurchenko, Ilya A. Novikov, Tatyana P. Makalish, Anatolii V. Kubyshkin, Oksana A. Andreeva, Anastasiya I. Bilyk
Summary: The main challenge in developing anti-coronavirus vaccines that target the virus's outer membrane proteins is the rapid variability in the pathogen's RNA genome. Affordable and quickly adaptable vaccine formulas are needed to address the emergence of new SARS-CoV-2 subtypes. This study evaluates the effectiveness of La-S-so-type adjuvant oligonucleotide vaccines on transgenic mice and shows that they increase the survival rate of animals infected with SARS-CoV-2 and reduce the destructive effects on lung tissue.
SCIENTIA PHARMACEUTICA
(2023)
Meeting Abstract
Cell Biology
Kseniya A. Yurchenko, Kateryna V. Laikova, Volodymyr V. Oberemok, Ilya A. Novikov, Alyona A. Yurchenko, Tatyana P. Makalish, Irina I. Fomochkina, Anatoly V. Kubyshkin
IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
(2022)
Article
Pathology
Iuliana Shramko, Elizaveta Ageeva, Eugene Krutikov, Konstantin Maliy, Irina Repinskaya, Iryna Fomochkina, Anatolii Kubishkin, Anna Gurtovaya, Cyrill Tarimov, Suman Shekhar
Summary: This study investigated the relationship between adiponectin and polymorphism in its gene receptors with the primary symptoms of pathogenesis in type 2 diabetes mellitus (DM2). The findings showed a strong correlation between rs16928751 polymorphism on the ADIPOR2 gene and increased body mass index (BMI), as well as associations between rs2275737 polymorphism on the ADIPOR1 gene and high levels of glycosylated hemoglobin (HbA1C) and stable hyperglycemia caused by rs2275738 polymorphism. Unique gene variants associated with the risk of developing DM2 were also identified in the Crimean population.