Article
Biochemistry & Molecular Biology
Xue-Hai Liang, Joshua G. Nichols, Cheryl Li De Hoyos, Hong Sun, Lingdi Zhang, Stanley T. Crooke
Summary: The Golgi apparatus plays a crucial role in the activity of PS-ASO drugs by facilitating the release of these compounds from endosomal organelles. Specific Golgi proteins such as Golgi-58K are shown to be involved in the transport and release of PS-ASOs, highlighting a novel function of Golgi proteins in mediating endosomal release of therapeutic oligonucleotides.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemical Research Methods
Martina Traykovska, Katya B. Popova, Robert Penchovsky
Summary: This study developed novel chimeric antisense oligonucleotides targeting glmS riboswitch and nagA mRNA to inhibit the growth of Staphylococcus aureus by blocking bacterial metabolic pathways. The specific targeting of glmS riboswitch was found to be sufficient to inhibit the bacterial growth, making it a promising target for antibacterial drug development using antisense oligonucleotides.
ACS SYNTHETIC BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Lukasz J. Kielpinski, Erik Daa Funder, Steffen Schmidt, Peter H. Hagedorn
Summary: This study investigates the interaction between phosphorothioate-modified antisense oligonucleotides and RNase H, revealing the necessity of Rp-PS groups for efficient cleavage and their alignment with the phosphate-binding pocket of RNase H. The chiral preference of RNase H for PS groups can guide cleavage to specific chemical bonds, leading to an optimization strategy for ASOs with increased knockdown activity.
NUCLEIC ACID THERAPEUTICS
(2021)
Review
Infectious Diseases
Nikolet Pavlova, Martina Traykovska, Robert Penchovsky
Summary: This article describes the rational design and applications of chimeric antisense oligonucleotides as antibacterial agents targeting riboswitches. By targeting specific riboswitches, the aim is to combat antibiotic-resistant bacteria and enhance the efficacy of antibacterial treatments. Experimental results demonstrate that these riboswitches are suitable targets for antibacterial drug development using antisense oligonucleotide technology.
Article
Biochemistry & Molecular Biology
Anna M. Rydzik, Dirk Gottschling, Eric Simon, Wioletta Skronska-Wasek, Joerg F. Rippmann, Doris Riether
Summary: The incorporation of N6-methyladenosine (m6 A) into siRNA targeting Factor VII affects its potency and selectivity in cells, reducing off-target effects. The position of m6 A in the siRNA duplex is crucial, as some sequences are found to be more potent and/or selective than their non-methylated counterparts. These findings suggest a potential regulatory role of N6-methyladenosine in the RNAi pathways and expand the scope of available chemical modifications for siRNA therapeutics.
Article
Infectious Diseases
Martina Traykovska, Robert Penchovsky
Summary: We described the design and application of a chimeric antisense oligonucleotide (ASO) called pVEC-ASO-1 as a novel antibacterial agent. By specifically degrading mRNA via RNase H, the pVEC-ASO-1 targets the S-adenosyl methionine (SAM)-I riboswitch found in Gram-positive bacteria, inhibiting bacterial growth.
Article
Biochemical Research Methods
Martina Traykovska, Robert Penchovsky
Summary: In recent decades, antibiotic drug resistance has become a significant challenge in modern medicine due to the emergence of bacteria strains resistant to known antibiotics. Riboswitches have emerged as novel targets for antibacterial drug discovery. This study describes the design and applications of antisense oligonucleotides as antibacterial agents targeting riboswitches, demonstrating their suitability for drug development.
ACS SYNTHETIC BIOLOGY
(2022)
Review
Medicine, Research & Experimental
Rong Dong, Bo Zhang, Biqin Tan, Nengming Lin
Summary: Macrophages play a crucial role in M2 polarization, which is regulated by various factors. Long non-coding RNAs (lncRNAs) are essential for the process, guiding macrophages towards an M2 phenotype through multiple mechanisms. Exosomal lncRNAs can also regulate polarization through paracrine action.
Article
Infectious Diseases
Shynar M. Maretbayeva, Anar S. Rakisheva, Malik M. Adenov, Lyazzat T. Yeraliyeva, Yerkebulan Zh. Algozhin, Assel T. Stambekova, Elmira A. Berikova, Askar Yedilbayev, Michael L. Rich, Kwonjune J. Seung, Assiya M. Issayeva
Summary: Rifampicin-resistant/multidrug-resistant (RR/MDR) and extensively drug-resistant (XDR) strains of M. tuberculosis are a serious public health issue in Kazakhstan. The approval of new TB drugs, bedaquiline and delamanid, offers hope for more effective MDR-TB treatment. A study of patients in Kazakhstan receiving bedaquiline or delamanid-containing regimen found that 89% experienced culture conversion within six months.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Layla R. Goddard, Charlotte E. Mardle, Hassan Gneid, Ciara G. Ball, Darren M. Gowers, Helen S. Atkins, Louise E. Butt, Jonathan K. Watts, Helen A. Vincent, Anastasia J. Callaghan
Summary: The increase in antibacterial resistance poses challenges for health and defense sectors, necessitating novel antibacterial targets and strategies. Targeting the translation initiation region of Escherichia coli rne mRNA using antisense oligonucleotides shows promise in inhibiting translation and facilitating RNase H-mediated mRNA cleavage.
Article
Multidisciplinary Sciences
Jiong Zhang, Xiangxiang Zhao, John R. Cappiello, Yi Yang, Yunfei Cheng, Guang Liu, Wenjing Fang, Yinzhu Luo, Yu Zhang, Jiajia Dong, Lixin Zhang, K. Barry Sharpless
Summary: A series of arylfluorosulfates synthesized via SuFEx, including compounds 3, 81, and 101, showed potent antibacterial activity, the ability to overcome multidrug resistance, and a lack of susceptibility to resistance development. These compounds also demonstrated rapid bactericidal potency, selectivity against gram-positive bacteria, and the capability to disrupt bacterial biofilms and kill persisters. Additionally, compound 3 exhibited synergy with streptomycin and gentamicin, while their anti-MRSA activity was evaluated using the Caenorhabditis elegans model.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Ysobel R. Baker, Cameron Thorpe, Jinfeng Chen, Laura M. Poller, Lina Cox, Pawan Kumar, Wooi F. Lim, Lillian Lie, Graham McClorey, Sven Epple, Daniel Singleton, Michael A. McDonough, Jack S. Hardwick, Kirsten E. Christensen, Matthew J. A. Wood, James P. Hall, Afaf H. El-Sagheer, Tom Brown
Summary: This study describes reduced-charge oligonucleotides containing artificial LNA-amide linkages, which have improved bioavailability and therapeutic efficacy, making it a potential new approach for treating untreatable diseases.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Sankha Pattanayak, Bhagyesh R. Sarode, Alexander Deiters, James K. Chen
Summary: Caged morpholino oligonucleotides (cMOs) are synthetic tools that allow light-inducible gene silencing in live organisms. A new caging strategy has been developed to enhance the efficacy of cMOs in zebrafish embryos.
Article
Biochemical Research Methods
Hiroyuki Takada, Keisuke Tsuchiya, Yosuke Demizu
Summary: This study developed helix-stabilized arginine-rich peptides and their conjugates with antisense phosphorodiamidate morpholino oligomers (PMOs) to investigate the relationships among peptide helicity, cellular uptake, and antisense activity.
BIOCONJUGATE CHEMISTRY
(2022)
Article
Nanoscience & Nanotechnology
Yan Zhang, Luogen Lai, Yijun Liu, Beini Chen, Jing Yao, Pengwu Zheng, Qingshan Pan, Wufu Zhu
Summary: In this study, GOx&HRP@ZIF-8/ASO nanomaterial was constructed using ZIF-8 material, achieving effective treatment of MRSA infection and filling the gap in the antibacterial application of biological enzymes.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Chemistry, Multidisciplinary
Svetlana V. Vasilyeva, Albina S. Petrova, Alexander A. Shtil, Dmitry A. Stetsenko
JOURNAL OF SAUDI CHEMICAL SOCIETY
(2020)
Article
Biochemistry & Molecular Biology
Yongdong Su, Patrick J. B. Edwards, Dmitry A. Stetsenko, Vyacheslav V. Filichev
Article
Biotechnology & Applied Microbiology
A. A. Ostrik, E. G. Salina, Y. Skvortsova, A. S. Grigorov, O. S. Bychenko, A. S. Kaprelyants, T. L. Azhikina
APPLIED BIOCHEMISTRY AND MICROBIOLOGY
(2020)
Correction
Biochemistry & Molecular Biology
S. A. Zhukov, S. V. Vasilyeva, A. A. Fokina, D. A. Stetsenko
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY
(2020)
Article
Multidisciplinary Sciences
Olga A. Patutina, Svetlana K. Gaponova (Miroshnichenko), Aleksandra Sen'kova, Innokenty A. Savin, Daniil Gladkikh, Ekaterine A. Burakova, Alesya A. Fokina, Mikhail A. Maslov, Elena Shmendel', Mattew J. A. Wood, Valentin V. Vlassov, Sidney Altman, Dmitry A. Stetsenko, Marina A. Zenkova
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Chemistry, Multidisciplinary
Alina Derzhalova, Oleg Markov, Alesya Fokina, Yasuo Shiohama, Timofei Zatsepin, Masayuki Fujii, Marina Zenkova, Dmitry Stetsenko
Summary: Novel lipid-conjugated DNA and RNA derivatives with low cytotoxicity and efficient cellular uptake without transfection agents were synthesized. Lipid-conjugated siRNAs targeting RGMa showed comparable gene silencing activity to unmodified control siRNA when delivered into cells via Lipofectamine-mediated transfection.
APPLIED SCIENCES-BASEL
(2021)
Article
Microbiology
Oksana Bychenko, Yulia Skvortsova, Rustam Ziganshin, Artem Grigorov, Leonid Aseev, Albina Ostrik, Arseny Kaprelyants, Elena G. Salina, Tatyana Azhikina
Summary: The expression of MTS1338 in non-pathogenic Mycobacterium smegmatis slows down their growth rate and increases their survival in macrophages. MTS1338 also affects the expression of proteins, the synthesis of cell wall components, and the regulation of iron metabolism and hypoxia response.
Article
Biochemistry & Molecular Biology
A. Hakobyan, E. A. Burakova, E. A. Arabyan, A. A. Fokina, A. R. Kotsinyan, S. V. Vasilyeva, O. S. Zakaryan, D. A. Stetsenko
Summary: The study evaluated the antiviral activity of antisense oligodeoxyribonucleotides targeting the main capsid protein VP72 mRNA of African swine fever virus. Two sequences of antisense oligonucleotides were identified that significantly reduced virus titer. The use of nanocomplexes showed higher antiviral effects compared to free oligonucleotides, indicating more efficient delivery to cells with Lipofectamine 3000.
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Suzan M. Hammond, Olga Sergeeva, Pavel A. Melnikov, Larissa Goli, Jessica Stoodley, Timofei S. Zatsepin, Dmitry A. Stetsenko, Matthew J. A. Wood
Summary: The study found that the splice-switching activity of 2'-MOE mesyl oligonucleotide was inferior to nusinersen in vivo, potentially due to compromised cellular uptake as indicated by the fluorescent confocal microscopy study in HEK293 cell line. This lower activity may be attributed to the compromised endosomal release and/or nuclear uptake of the 2'-OMe or 2'-MOE mu- and beta-oligonucleotides compared to their phosphorothioate analog.
NUCLEIC ACID THERAPEUTICS
(2021)
Article
Biochemistry & Molecular Biology
Nadezhda S. Dyrkheeva, Aleksandr S. Filimonov, Olga A. Luzina, Kristina A. Orlova, Irina A. Chernyshova, Tatyana E. Kornienko, Anastasia A. Malakhova, Sergey P. Medvedev, Alexandra L. Zakharenko, Ekaterina S. Ilina, Rashid O. Anarbaev, Konstantin N. Naumenko, Kristina Klabenkova, Ekaterina A. Burakova, Dmitry A. Stetsenko, Suren M. Zakian, Nariman F. Salakhutdinov, Olga Lavrik
Summary: This study describes the synthesis and evaluation of compounds that efficiently suppress TDP1 activity, with some showing synergistic effects when combined with the TOP1 inhibitor topotecan. The structure of heterocyclic substituents introduced into the compounds affects their TDP1 inhibitory efficiency. Some compounds not only inhibit TDP1, but also show potential inhibition of TDP2 and/or PARP1 at higher concentration ranges.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Maxim S. Kupryushkin, Anton Filatov, Nadezhda L. Mironova, Olga A. Patutina, Ivan Chernikov, Elena L. Chernolovskaya, Marina A. Zenkova, Dmitrii Pyshnyi, Dmitry A. Stetsenko, Sidney Altman, Valentin V. Vlassov
Summary: Antisense gapmer oligonucleotides containing phosphoryl guanidine (PG) groups were successfully synthesized and shown to have increased nuclease resistance in serum-containing medium. Replacing two internucleotidic phosphates with PG groups did not decrease cellular uptake, and increasing the number of PG groups affected cellular uptake.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Oncology
Svetlana Gaponova, Olga Patutina, Aleksandra Sen'kova, Ekaterina Burakova, Innokenty Savin, Andrey Markov, Elena Shmendel, Mikhail Maslov, Dmitry Stetsenko, Valentin Vlassov, Marina Zenkova
Summary: Current approaches to cancer treatment lack efficiency and selectivity, causing non-specific toxic effects. This study demonstrates the potential of highly selective antisense downregulation of microRNAs as a targeted therapy for oncological diseases. Combinations of oligonucleotides targeted to specific microRNAs effectively inhibit tumor growth and metastasis without causing toxic effects in vivo.
Review
Biochemistry & Molecular Biology
Kristina Klabenkova, Alesya Fokina, Dmitry Stetsenko
Summary: This article discusses the importance of peptide-oligonucleotide conjugates in enhancing the efficiency of therapeutic nucleic acids and the related chemical synthesis methods, which are mainly divided into two strategies: stepwise solid-phase synthesis and post-synthetic conjugation.
Article
Biochemistry & Molecular Biology
A. A. Fokina, Yu E. Poletaeva, E. A. Burakova, A. Yu Bakulina, T. S. Zatsepin, E. Ryabchikova, D. A. Stetsenko
Summary: The study introduces a template-assisted method for 3D assembly of nucleic acid nanostructures, utilizing branched oligonucleotides as templates and building blocks to assemble DNA nanostructures.
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY
(2021)
Article
Agriculture, Multidisciplinary
A. A. Ostanin, O. Y. Leplina, E. A. Burakova, T. Tyrinova, A. A. Fokina, A. S. Proskurina, S. S. Bogachev, D. A. Stetsenko, E. R. Chernykh
VAVILOVSKII ZHURNAL GENETIKI I SELEKTSII
(2020)