Article
Chemistry, Medicinal
Hongqian Ren, Liya Song, Wei Zhang, Liang Xu
Summary: This study presents a general strategy to construct stapled cyclic structures of ASONs with stimuli-responsive features, allowing for cleavage in the reducing microenvironment of tumor cells. The stapled structures enhanced anti-tumor activity compared to linear counterparts, providing a new and effective strategy for designing nucleic acid based therapeutics.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Medicine, Research & Experimental
Zhe Zhang, Hongqian Ren, Zuyi Chen, Yaling Zhang, Zhuolin Zhang, Yuan Luo, Shiyuan Wang, Xuesong Feng, Liang Xu
Summary: This study presents a novel prodrug-type design for antisense oligonucleotides (ASONs), which features a dumbbell conformation and a responsive disulfide switch, improving the stability and antitumor activity of ASONs.
MOLECULAR PHARMACEUTICS
(2022)
Review
Pharmacology & Pharmacy
Shivam Kumar Pandey, Rakesh Kumar Singh
Summary: Parkinson's disease is a common neurodegenerative disease that currently can only be managed symptomatically. Nucleic acid-based therapies, such as antisense oligonucleotides and gene therapy, show promise in regulating the genetic dysregulation associated with the disease, specifically the downregulation of the alpha-synuclein gene. This review examines the advancements and limitations of nucleic acid-based therapies for Parkinson's disease.
FRONTIERS IN PHARMACOLOGY
(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)
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
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)
Article
Biochemistry & Molecular Biology
Norihito Sugimoto, Junsuke Hayashi, Ryohei Funaki, Shun-ichi Wada, Fumito Wada, Mariko Harada-Shiba, Hidehito Urata
Summary: Various types of oligonucleotides containing linear disulfides were synthesized and their conversion rates under reducing conditions were evaluated. The structural requirements for the conversion of linear disulfide-modified oligonucleotides were elucidated. The modification enhances the stability of oligonucleotides in serum and promotes their cellular uptake.
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
Multidisciplinary Sciences
Taiki Tsurusaki, Kazuki Sato, Hiroki Imai, Kunihiro Hirai, Daisuke Takahashi, Takeshi Wada
Summary: Phosphorodiamidate morpholino oligonucleotides (PMOs) are a promising type of antisense oligonucleotides, but their challenging synthesis makes them difficult to access. This research presents an efficient synthetic approach for PMOs using the H-phosphonate approach. The use of phosphonium-type condensing reagents significantly reduced coupling times compared with the current synthetic approach. This approach would facilitate the large-scale synthesis of PMOs and accelerate their popularity and accessibility as a next-generation therapy.
SCIENTIFIC REPORTS
(2023)
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
Clinical Neurology
Alexandra Litvinchuk, Tien-Phat Huynh, Yang Shi, Rosemary J. Jackson, Mary B. Finn, Melissa Manis, Caroline M. Francis, Ainsley C. Tran, Patrick M. Sullivan, Jason D. Ulrich, Bradley T. Hyman, Tracy Cole, David M. Holtzman
Summary: Therapeutic reduction of ApoE4 levels through ASO treatment showed significant protective effects on tau pathology, neurodegeneration, neuroinflammation, and synaptic density, indicating a potential therapeutic approach for APOE4 carriers with tauopathy, including Alzheimer's disease.
ANNALS OF NEUROLOGY
(2021)
Article
Multidisciplinary Sciences
Sneha Shah, Kevin J. Sharp, Sithara Raju Ponny, Jonathan Lee, Jonathan K. Watts, Elizabeth Berry- Kravis, Joel D. Richter
Summary: Aberrant alternative splicing of mRNAs leads to dysregulated gene expression in neurological disorders, such as fragile X syndrome (FXS). In this study, the researchers found hundreds of incorrectly expressed and spliced mRNAs in the blood and brain tissues of FXS individuals. They also discovered a previously unknown RNA isoform, FMR1-217, which is generated through mis-splicing of the FMR1 gene in FXS tissues. Treatment with antisense oligonucleotides (ASOs) could reduce FMR1-217 and restore normal gene expression and protein levels. These findings suggest that RNA-processing events in blood could serve as biomarkers for FXS and ASO treatment may be a potential therapy.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Chemistry, Analytical
Zifan Li, Fei Tong, Li Xiao, Nicholas R. Larson, Xuan Zhou, Yueheng Zhang, Jonas P. Immel-Brown, George M. Bou-Assaf
Summary: This study presents a novel protocol for detecting stereochemical changes in phosphorothioate oligonucleotides, using nuclease P1 digestion followed by LCMS analysis. The method is valuable for establishing stereochemical comparability and ensuring manufacturing consistency of oligonucleotide therapeutics.
Review
Biochemistry & Molecular Biology
Craig S. McIntosh, Dunhui Li, Steve D. Wilton, May T. Aung-Htut
Summary: Polyglutamine (polyQ) ataxias are a group of neurological disorders caused by expanded CAG trinucleotide repeats, mainly characterized by progressive ataxia. These disorders are characterized by neuronal aggregations and share common pathogenic mechanisms, with limited therapeutic options available to slow or stop disease progression.
Article
Materials Science, Biomaterials
Liang Xu, Tao Zhang, Huajin Dong, Dazheng Cai, Han Han, Qingbin Meng, Yongjia Tang, Qingguo Meng, Zehui Gong, Tianhong Zhang, Zhenqing Zhang, Husheng Yan, Keliang Liu
JOURNAL OF MATERIALS CHEMISTRY B
(2016)
Article
Chemistry, Medicinal
Yongjia Tang, Zeye Han, Jiamei Guo, Yangli Tian, Keliang Liu, Liang Xu
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2018)
Article
Materials Science, Biomaterials
Tao Zhang, Yongjia Tang, Wei Zhang, Shan Liu, Yumei Zhao, Wei Wang, Jian Wang, Liang Xu, Keliang Liu
JOURNAL OF MATERIALS CHEMISTRY B
(2018)
Article
Pharmacology & Pharmacy
Yongjia Tang, Zeye Han, Hongqian Ren, Jiamei Guo, Huihui Chong, Yangli Tian, Keliang Liu, Liang Xu
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2018)
Article
Materials Science, Biomaterials
Tao Zhang, Zeye Han, Wei Zhang, Jian Wang, Liang Xu
INTERNATIONAL JOURNAL OF POLYMERIC MATERIALS AND POLYMERIC BIOMATERIALS
(2020)
Article
Immunology
Jing Wu, Shuang Li, Tete Li, Xinping Lv, Mingyou Zhang, Guoxia Zang, Chong Qi, Yong-Jun Liu, Liang Xu, Jingtao Chen
JOURNAL OF IMMUNOLOGY RESEARCH
(2019)
Editorial Material
Immunology
Lei Zhao, Jianjun Zhang, Liang Xu, Hussein A. Abbas
JOURNAL OF IMMUNOLOGY RESEARCH
(2019)
Article
Immunology
Liang Xu, Zeye Han, Hongqian Ren
Summary: This study successfully synthesized a conjugate of DNA-oligopeptide to improve the anti-fusion activity of DNA G-quadruplex-based inhibitors against HIV-1. The conjugate G1 showed enhanced anti-cell-cell fusion activity compared to quadruplex without MT hook, demonstrating the importance of structure-activity relationships in DNA helix-based inhibitors.
CURRENT HIV RESEARCH
(2021)
Article
Medicine, Research & Experimental
Zhe Zhang, Hongqian Ren, Zuyi Chen, Yaling Zhang, Zhuolin Zhang, Yuan Luo, Shiyuan Wang, Xuesong Feng, Liang Xu
Summary: This study presents a novel prodrug-type design for antisense oligonucleotides (ASONs), which features a dumbbell conformation and a responsive disulfide switch, improving the stability and antitumor activity of ASONs.
MOLECULAR PHARMACEUTICS
(2022)
Article
Pharmacology & Pharmacy
Zhe Zhang, Zuyi Chen, Cheng Li, Zhenyu Xiao, Yuan Luo, Xiaochen Pan, Liang Xu, Xuesong Feng
Summary: This study introduces a new category of antisense oligonucleotides (ASONs) for cancer therapy, utilizing anisamide conjugation at phosphorothioate sites. The conjugation sites and ligand amount have an impact on anti-enzymatic stability and cellular uptake, altering the antitumor activity. The optimal conjugate, with double anisamide (T6), was identified and further examined for its antitumor activity and mechanism in vitro and in vivo. This paper presents a novel strategy for nucleic acid-based therapeutics with improved drug delivery, biophysical properties, and biological efficacy.
Article
Chemistry, Multidisciplinary
Zuyi Chen, Zhe Zhang, Shuangshuang Liu, Zhenyu Xiao, Yuan Luo, Liang Xu, Xuesong Feng
Summary: In this paper, a novel strategy of chimeric 4A2-5-ASON prodrug combined with chemotherapy for oncotherapy was proposed to address the issues of rapid degradation and limited therapeutic efficacy in native antisense oligonucleotides (ASONs) development. The self-assembled hairpin-end prodrug structure provided a DOX loading site, while enhancing stability against nuclease degradation. The disulfide led responsive drug release and effective therapeutic effects were achieved through the combined action of RNase H and RNase L recruitment, along with chemotherapy drug Doxorubicin (DOX), in both in vitro and in vivo experiments.
CHEMICAL COMMUNICATIONS
(2023)
Article
Materials Science, Biomaterials
Jia Wang, Xia Tian, Wei Zhang, Xiao Dong, Zhanguang Wang, Shiyuan Wang, Yonghan Liang, Wei Wang, Liang Xu, Yunlan Li
Summary: This study demonstrates a composite system composed of butyl cyanoacrylate, triethyl citrate, and nanosilica that exhibits blood/wet-adhesion capability as a new sealing glue. The composite system showed good physical and chemical properties in vitro, and safety assays indicated good biocompatibility. In animal models, it exhibited effective closure. These findings suggest promising potential for clinical applications and provide a new strategy for designing underwater adhesive agents and other biomaterials for wet conditions.
JOURNAL OF MATERIALS CHEMISTRY B
(2023)
Article
Materials Science, Biomaterials
Liya Song, Pengfei Chen, Jin Yu, Xiaolu Han, Yabing Hua, Shan Liu, Bo Pang, Jing Gao, Jiahua Ma, Liang Xu
Summary: A novel oral drug delivery system based on poly-cyanoacrylate and hydroxypropyl methylcellulose phthalate was developed for intestinal targeting and sustained drug release. The system showed good intestinal targeting and sustained drug release both in vitro and in vivo. This system improved the bioavailability of the model drug and demonstrated desirable anti-atherosclerosis efficacy in a rabbit model.
JOURNAL OF MATERIALS CHEMISTRY B
(2021)
Article
Pharmacology & Pharmacy
Xuezhi Zhuo, Vito Fodera, Per Larsson, Zarah Schaal, Christel A. S. Bergstrom, Korbinian Lobmann, Aleksei Kabedev
Summary: Our previous work demonstrated that beta-lactoglobulin-stabilized amorphous solid dispersion (ASD) loaded with 70 % indomethacin remains stable for over 12 months. We further investigated the stabilization mechanisms by testing five other drug molecules and using experimental techniques and molecular dynamics simulations. The results showed that steric confinement, hydrogen bonding, and the glass transition temperature of the drug molecule play important roles in stabilizing ASDs with high drug loadings.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Sebastian Schmidt, Ulrike Holzgrabe
Summary: The binding of drugs to plasma proteins, such as human serum albumin (HSA), is crucial for determining pharmacokinetic parameters. This study investigated the enantioselective binding of S- and R-ketamine to HSA. It was found that ketamine has weak affinity to HSA, with no significant differences in binding behavior between the individual enantiomers and the racemate. The aromatic ring and N-methyl group were identified as the most strongly involved structural moieties in the binding of ketamine to HSA.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Yuchen Zhao, Han Wang, Lin Jin, Ziwei Zhang, Lianghu Liu, Mengqi Zhou, Xianzheng Zhang, Lingling Zhang
Summary: Interleukins (ILs) are important for communication between immune cells and non-immune cells, but dysregulation of ILs expression is a characteristic of autoinflammatory diseases. Drugs targeting ILs have significant clinical benefits, but may also cause adverse reactions. Fusion protein technology, with its ability to enhance therapeutic efficacy, has been explored for developing anti-inflammatory drugs. This review discusses the efficacy of fusion protein drugs developed with ILs or their receptors in treating autoinflammatory diseases, highlighting the potential of this technology in future anti-inflammatory drug development.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Serena Bertoni, Elena Simone, Stefano Sangiorgi, Beatrice Albertini, Nadia Passerini
Summary: This study investigated the correlation between the structure and release properties of solid lipid microparticles (MPs) with different liquid additives. The additives accelerated the conversion of the unstable alpha-form of tristearin to the stable beta-polymorph and caused structural modifications in the MPs. The presence of additives prolonged the drug release in water and resulted in higher release profiles in biorelevant media. The findings suggest that the release behavior can be influenced by the polymorphism and supramolecular-level structural modification of lipid formulations containing crystal modifiers.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Juulia Jarvinen, Ahmed B. Montaser, Santosh Kumar Adla, Jukka Leppanen, Marko Lehtonen, Kati-Sisko Vellonen, Tuomo Laitinen, Aaro Jalkanen, William F. Elmquist, Juri Timonen, Kristiina M. Huttunen, Jarkko Rautio
Summary: This study attempted to alter the brain distribution pattern of Palbociclib by creating and assessing two novel prodrugs. Although the prodrug design did not significantly improve Palbociclib brain delivery, the study provides valuable insights for future prodrug development and drug delivery strategies targeting specific transporters.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Review
Pharmacology & Pharmacy
Miao Wang, Xinyu Ma, Shiyu Zong, Yaqiong Su, Rui Su, Hong Zhang, Yang Liu, Chunliu Wang, Ye Li
Summary: This article discusses the potential and limitations of nasal administration in central nervous system drug delivery. Nasal gel viscosity can alleviate the impact of nasal mucociliary clearance on drug delivery, and materials such as gellan gum, chitosan, carbomer, cellulose, and poloxamer can be used to prepare nasal gels.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Bjarke Strom Larsen, Eric Kissi, Liebert Parreiras Nogueira, Natalja Genina, Ingunn Tho
Summary: This study investigates the influence of drug load and polymer molecular weight on the structure of 3D printed tablets. The results show that drug load and polymer molecular weight have a significant impact on the porosity and size of the tablets, while the effect of drug load on the total porosity of the tablets is minimal.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Zhentao Qiao, Fuhang Wang, Dongjian Han, Yuansong Zhuang, Qingjiao Jiang, Yi Zhang, Miaomiao Liu, Quanxu An, Zhiwei Wang, Deliang Shen
Summary: In this study, it was demonstrated that periadventitial delivery of rapamycin-fibrin glue (RPM-FG) can inhibit intimal hyperplasia (IH) in a rat carotid artery injury model without compromising re-endothelialization. This provides a promising direction for the future development of a safe, effective, and minimally invasive perivascular drug delivery method to treat vascular disease.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Neele Puhlmann, Rodrigo Vidaurre, Klaus Kuemmerer
Summary: Active pharmaceutical ingredients and their metabolites and transformation products are pollutants that can harm human and environmental health. Designing greener APIs is an effective strategy to address this issue. The drug discovery and development process can incorporate environmental parameters to achieve this design, and this process is highly flexible.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
