Review
Chemistry, Multidisciplinary
Roberto El-Khoury, Masad J. Damha
Summary: FANA is an ideal tool for mimicking DNA secondary structures and probing biomolecular interactions, showing high binding affinity and implications in therapeutics. It also holds promise in stabilizing noncanonical DNA structures and playing a role in biological research.
ACCOUNTS OF CHEMICAL RESEARCH
(2021)
Article
Multidisciplinary Sciences
Jiaxuan Chen, Dandan Zhu, Baoping Lian, Kangjie Shi, Peng Chen, Ying Li, Wenyi Lin, Ling Ding, Qiulin Long, Yang Wang, Erik Laurini, Wenjun Lan, Yun Li, Aura Tintaru, Caoyun Ju, Can Zhang, Sabrina Pricl, Juan Iovanna, Xiaoxuan Liu, Ling Peng
Summary: Nucleic acid therapeutics serve as an important drug modality for targeting undruggable targets, responding to evolving pathogens, and precision medicine at the gene level. Dendrimers, as precision delivery systems, have been utilized for selective and on-demand delivery of DNA and siRNA. The properties and performance of these dendrimers were systematically studied, and they exhibited cargo-adaptive and selective delivery, tumor targeting, and redox-responsive cargo release. The dendrimers outperformed currently available vectors in tumor and cancer cell-specific delivery of siRNA and DNA therapeutics in various cancer models. This study provides a pathway for engineering tailor-made vectors for nucleic acid delivery and precision medicine.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Chemistry, Multidisciplinary
Yuliya Dantsu, Ying Zhang, Wen Zhang
Summary: The fluoro-modification at the 2'-position of L-cytidine in L-nucleic acids does not disrupt their thermostabilities and maintains structural integrity, allowing it to form a Watson-Crick base pair with L-guanosine. This provides a useful biochemical strategy for investigating L-nucleic acids in advanced molecular therapy.
Article
Chemistry, Physical
Paul M. DeMent, Chenlu Liu, Joseph Wakpal, Richard N. Schaugaard, H. Bernhard Schlegel, Hien M. Nguyen
Summary: Phenanthroline is a commonly used bidentate ligand in coordination chemistry, which can be tuned to develop efficient and stereoselective catalysts. By activating 2-deoxy-2-fluoro glycosyl halides with phenanthroline-based catalysts, glycosylations with high levels of alpha-selectivities and moderate to high yields can be achieved. The proposed mechanism for this catalytic glycosylation system involves double S(N)2 displacement pathways with phenanthroline catalysts, ensuring stereoselective formation of alpha-1,2-cis-2-fluoro glycosides.
Article
Chemistry, Organic
Yuliya Dantsu, Ying Zhang, Wen Zhang
Summary: In this study, a chemically derivatized 2'-deoxy-2'-fluoro-L-uridine building block was synthesized and incorporated into oligonucleotides. Thermo-denaturization and enzymatic digestion experiments showed superior stability of the modified molecules. The crystal structure of L-type fluoro-DNA was determined, revealing increased L-helix stability through fluoro-modification and laying the foundation for potential functional applications.
Article
Biochemical Research Methods
Filipa Mota, Patricia De Jesus, Sanjay K. Jain
Summary: Researchers developed a method to synthesize F-18-FDS for positron emission tomography imaging to visualize infections. Clinical study in 26 patients showed that F-18-FDS PET was safe and could differentiate infections caused by Enterobacterales from other pathologies such as sterile inflammation or cancer.
Article
Chemistry, Multidisciplinary
Yuliya Dantsu, Wen Zhang
Summary: This study reports the synthesis and incorporation of a novel 2'-methoxy-modified L-cytidine analog into oligonucleotides. The modified L-nucleic acids show enhanced thermostability and form Watson-Crick base pairs with L-guanosine. This chemically modified L-cytidine provides a useful strategy to create mirror-image nucleic acid molecules with expanded functionalities.
Article
Nanoscience & Nanotechnology
Can Luo, Yuqi Xie, Minze He, Yazhou Li, Yinghao Xia, Lei He, Jili Li, Linlin Wang, Xiaoyan Han, Lili Zhang, Xi Yuan, Zhiqiang Wang, Yanlan Liu, Weihong Tan
Summary: This study introduces a new concept of amphiphilic nucleic acids (ANAs) as a cation-free nucleic acid delivery platform. The ANAs platform demonstrates high siRNA loading capacity, rapid cellular uptake, efficient endosomal escape, and remarkable gene silencing and synergistic inhibitory effects on cancer cells.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Review
Rheumatology
Manil Subesinghe, Shaheel Bhuva, Nikita Arumalla, Andrew Cope, David D'Cruz, Sujith Subesinghe
Summary: 2-deoxy-2[F-18]fluoro-D-glucose (FDG) PET-CT has revolutionized oncological imaging, and it is also widely used in the diagnosis and treatment of infectious and inflammatory diseases. Rheumatological diseases, which can affect multiple sites within the musculoskeletal system, can be accurately diagnosed and treated using FDG PET-CT.
Article
Chemistry, Medicinal
Mieke Guinan, Ningwu Huang, Mark Smith, Gavin J. Miller
Summary: The study developed a new class of nucleoside analogues with good activity against Hepatitis C replicon, which is significant in the field of antiviral drug research.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Pharmacology & Pharmacy
Claudia Lotter, Claudio Luca Alter, Jan Stephan Bolten, Pascal Detampel, Cornelia G. Palivan, Tomaz Einfalt, Jorg Huwyler
Summary: In this study, phosphatidylserine (PS) was incorporated into non-viral lipid nanoparticle (LNP) DNA/RNA constructs in a virus-inspired biomimetic approach to enhance cellular transfection. The results showed that PS-decorated LNPs exhibited significantly increased transgene expression in vitro and enhanced transfection efficiency in vivo. This method provides a new avenue for efficient gene therapy and can be extended to other therapeutic systems.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2022)
Article
Polymer Science
Tieshuai Zhao, Ben Drain, Gokhan Yilmaz, C. Remzi Becer
Summary: In this study, pentafluoro benzyl bromide was used as a clickable initiator for the cationic ring opening polymerization of poly(2-oxazolines) to synthesize various multiblock copolymers. By combining the para-fluoro-thiol click reaction with terminating agents in a one-pot approach, multiblock copolymers such as PEtOx-mb-PMeOx were successfully prepared. Characterization of the polymers was done using SEC, H-1 NMR, and MALDI-ToF mass spectrometry, and the self-assembly properties were studied using DLS and TEM, which showed nanoparticles with diameters ranging from 184 nm to 250 nm for the PEtOx-mb-PMeOx copolymers.
Article
Biochemistry & Molecular Biology
Nicole L. Welch, Meilin Zhu, Catherine Hua, Juliane Weller, Marzieh Ezzaty Mirhashemi, Tien G. Nguyen, Sreekar Mantena, Matthew R. Bauer, Bennett M. Shaw, Cheri M. Ackerman, Sri Gowtham Thakku, Megan W. Tse, Jared Kehe, Marie-Martine Uwera, Jacqueline S. Eversley, Derek A. Bielwaski, Graham McGrath, Joseph Braidt, Jeremy Johnson, Felecia Cerrato, Gage K. Moreno, Lydia A. Krasilnikova, Brittany A. Petros, Gabrielle L. Gionet, Ewa King, Richard C. Huard, Samantha K. Jalbert, Michael L. Cleary, Nicholas A. Fitzgerald, Stacey B. Gabriel, Glen R. Gallagher, Sandra C. Smole, Lawrence C. Madoff, Catherine M. Brown, Matthew W. Keller, Malania M. Wilson, Marie K. Kirby, John R. Barnes, Daniel J. Park, Katherine J. Siddle, Christian T. Happi, Deborah T. Hung, Michael Springer, Bronwyn L. MacInnis, Jacob E. Lemieux, Eric Rosenberg, John A. Branda, Paul C. Blainey, Pardis C. Sabeti, Cameron Myhrvold
Summary: A microfluidic CRISPR-based platform called mCARMEN enables multiplexed and high-throughput identification of a wide range of respiratory viruses, including specific SARS-CoV-2 variants. The platform combines cost-effectiveness, diagnostic-grade performance, and a streamlined workflow for clinical use.
Article
Virology
Irani Alves Ferreira-Bravo, Jeffrey J. DeStefano
Summary: Aptamers generated using SELEX method with FANA show high affinity to RBD and S1 domains of SARS-CoV-2, directly blocking their interaction with ACE2, exhibiting high specificity and affinity similar to previous DNA aptamers.
Article
Biotechnology & Applied Microbiology
Wei Liu, Shan Yuan, Miaomiao Jin, Mo Xian
Summary: Fluorine is an essential element in medicine, agriculture, and materials design, as it can enhance the functionality and performance of organic compounds. However, fluorine is rarely found in natural metabolism. Researchers have developed a new biosynthetic strategy to expand the molecular space by synthesizing 2-fluoro-3-hydroxypropionic acid (2-F-3-HP). This biocatalytic method offers significant advantages in terms of environmental and safety impacts.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Alice Ghidini, Antoine Clery, Francois Halloy, Frederic H. T. Allain, Jonathan Hall
Summary: RNA-PROTACs represent a novel approach for targeting RBPs by using small RNA mimics to induce proteasomal degradation, potentially holding promise for applications in cancer cells.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Christian Berk, Yuluan Wang, Artur Laski, Stylianos Tsagkris, Jonathan Hall
Summary: Identifying the targetome of a microRNA is crucial for understanding its functions. A new CLIP method that does not require 5'-phosphorylation for ligation has been introduced by using chemically synthesized microRNAs with 2'-, 3'-cyclic phosphate groups. By optimizing the chemistry underlying ligation, the basis for an improved method to identify miRNA targetomes has been provided.
Article
Engineering, Biomedical
Britta Franziska Hettich, Johannes Josua Bader, Jean-Christophe Leroux
Summary: Different methods were explored to incorporate hydrophilic non-membrane permeable compounds into stem cell-derived small EV, with freeze-thawing and osmotic shock proving to be the most appropriate methods for high drug encapsulation while preserving structural and biological vesicle characteristics.
ADVANCED HEALTHCARE MATERIALS
(2022)
Article
Chemistry, Multidisciplinary
Yinyin Bao, Nevena Paunovic, Jean-Christophe Leroux
Summary: Vat photopolymerization technique has shown great potential in the fabrication of medical implants and devices. However, the conflicting viscosity requirements for printing resins present a challenge. Heat-assisted DLP and volumetric printing techniques offer new possibilities by enabling the fabrication of complex and personalized biodegradable structures and circumventing the need for low viscosity resins.
ADVANCED FUNCTIONAL MATERIALS
(2022)
Article
Chemistry, Multidisciplinary
Alyssa C. Hill, Daniel van Leeuwen, Verena Schlosser, Alok Behera, Bogdan Mateescu, Jonathan Hall
Summary: RNA interference (RNAi) mediated by siRNA-3WJ, which is a fusion of siRNA with the phi29 3WJ motif, can enter the RNAi pathway through Dicer cleavage and achieve gene silencing. It has been found that siRNA-3WJs are effective even in Dicer-deficient or Argonaute 2-deficient cells, and they work best when the antisense strand of the siRNA duplex is positioned 5' of the 3WJ.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Oncology
Meriem Messaoudene, Reilly Pidgeon, Corentin Richard, Mayra Ponce, Khoudia Diop, Myriam Benlaifaoui, Alexis Nolin-Lapalme, Florent Cauchois, Julie Malo, Wiam Belkaid, Stephane Isnard, Yves Fradet, Lharbi Dridi, Dominique Velin, Paul Oster, Didier Raoult, Francois Ghiringhelli, Romain Boidot, Sandy Chevrier, David T. Kysela, Yves Brun, Emilia Liana Falcone, Genevieve Pilon, Florian Plaza Onate, Oscar Gitton-Quent, Emmanuelle Le Chatelier, Sylvere Durand, Guido Kroemer, Arielle Elkrief, Andre Marette, Bastien Castagner, Bertrand Routy
Summary: The study demonstrates that oral supplementation with polyphenol-rich berry camu-camu alters gut microbial composition in mice, leading to antitumor activity and enhanced anti-PD-1 response. The active compound castalagin enriches for specific bacteria and induces metabolic changes to support immunotherapy efficacy.
Article
Chemistry, Multidisciplinary
Michael Burger, Seraina Kaelin, Jean-Christophe Leroux
Summary: Non-viral gene delivery agents mainly rely on charge-based and hydrophobic interactions, while the human protein TFAM utilizes specific protein-protein and protein-DNA interactions to form nanoparticles with DNA. In this study, TFAM's properties are repurposed to create a DNA transfection agent through protein engineering. The TFAM/DNA complexes are stabilized by introducing cysteine point mutations and covalently fusing with other proteins to enable endosomal escape and DNA protection. This TFAM-based DNA scaffold shows promising activity in transfecting cells.
Article
Chemistry, Multidisciplinary
Nicole Kleger, Simona Fehlmann, Seunghun S. Lee, Cyril Denereaz, Martina Cihova, Nevena Paunovic, Yinyin Bao, Jean-Christophe Leroux, Stephen J. Ferguson, Kunal Masania, Andre R. Studart
Summary: This article reports a universal manufacturing platform that utilizes photocurable resins and printed salt structures as leachable molds to shape materials into complex geometries. Through systematic investigation of the printing, debinding, and sintering steps, suitable ink formulations for crack-free salt templates are identified. By infiltrating the sintered molds and leaching the templates, complex-shaped architectures are created from various compositions.
ADVANCED MATERIALS
(2022)
Article
Multidisciplinary Sciences
Malgorzata M. Duszczyk, Harry Wischnewski, Tamara Kazeeva, Rajika Arora, Fionna E. Loughlin, Christine von Schroetter, Ugo Pradere, Jonathan Hall, Constance Ciaudo, Frederic H. -T. Allain
Summary: DND1 is an RNA-binding protein essential for germline development, mediating its function through a non-canonical AU-rich RNA recognition mode by the tandem RRMs, while the dsRBD plays a role in recruiting effector complexes for target regulation. The authors report an unusual mode of AU-rich RNA recognition by the RRMs of DND1 in a 27.5 kDa NMR structure and provide additional insight on DND1 function from cell-based experiments.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Olivia Lui, Lharbi Dridi, Emmanuel Gonzalez, Suraya Yasmine, Ryszard Kubinski, Hannah Billings, Joerg Bohlmann, Stephen G. Withers, Corinne Maurice, Bastien Castagner
Summary: The effects of alpha-amylase inhibitors on glycan metabolism in human gut bacteria need further investigation.
ACS CHEMICAL BIOLOGY
(2023)
Review
Chemistry, Multidisciplinary
Alyssa C. Hill, Jonathan Hall
Summary: This article summarizes the synthesis of 2'-O-alkylated ribonucleosides for use in therapeutic antisense oligonucleotides (ASOs). The synthesis involves substituting the ribose 2'-OH group with 2'-ethylene glycol derivatives. The resulting MOE-modified oligonucleotides show improved properties, such as higher affinity and specificity for RNA substrates, as well as increased stability to nucleases.
HELVETICA CHIMICA ACTA
(2023)
Article
Engineering, Biomedical
Elita Montanari, Hanna Krupke, Jean-Christophe Leroux
Summary: Currently, there is a lack of sustained release formulations for highly dosed small hydrophilic drugs. In this study, parenteral lipid spherulites were developed to entrapped and release large amounts of such drugs in a sustained manner. The spherulites demonstrated higher loading efficiency compared to liposomes and showed promising results in increasing the systemic exposure of the drug. PE spherulites were found to be a promising lipid platform for the extravascular administration of highly dosed small hydrophilic drugs.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Cell Biology
Zhi Luo, David Klein Cerrejon, Simon Romer, Nicole Zoratto, Jean-Christophe Leroux
Summary: Biopharmaceuticals, such as proteins and peptides, have greatly improved the treatment of various diseases. However, most of these drugs need to be administered parenterally due to their large size and instability. In this study, a novel technology was developed to enhance drug absorption by combining noninvasive stretching of the buccal mucosa with permeation enhancers. The engineered suction patch achieved significantly higher bioavailability in dogs compared to a commercial tablet formulation of a peptide drug. Additionally, a first-in-human study confirmed the acceptability of this dosage form, supporting its clinical translatability.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Chemistry, Multidisciplinary
Jonathan Hall, Anastasia Ashkinadze, Jan Philipp Becker, Artur Laski, Eva-Maria Manz, Stefan Moravcik, Sebastian Sjoestroem, Mathilde Vincent
Summary: The oligonucleotide therapeutics field has experienced rapid development in recent years, with thirteen approved drugs and the potential for further growth in the future. Progress in this field is attributed to advancements in oligonucleotide medicinal chemistry and careful selection of molecular targets and disease areas.
Article
Polymer Science
Nevena Paunovic, Jean-Christophe Leroux, Yinyin Bao
Summary: A dual-polymer resin formulation is proposed for digital light processing of biodegradable elastomers with mechanical properties comparable to Sylgard-184.