Article
Chemistry, Multidisciplinary
Yaoxuan Chen, Rupeng Zhao, Lele Li, Yuliang Zhao
Summary: This study develops a near-infrared light-controlled DNAzyme delivery platform, which enhances the gene-silencing efficacy by improving the endosomal escape capability. The nanoplatform integrates DNAzyme-based gene therapy with NIR light-triggered photodynamic therapy for combinational tumor treatment.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Jing Wang, Shanshan Yu, Qiong Wu, Xue Gong, Shizhen He, Jinhua Shang, Xiaoqing Liu, Fuan Wang
Summary: We designed a self-catabolic DNA nanocapsule for sustained activation of therapeutic DNAzyme in cancer cells, utilizing a hierarchical rolling circle replication (RCR) nanostructure. Through tumor-anchoring aptamer strands, the nanocapsule was specifically accumulated in cancer cells and sequentially activated for gene silencing. By employing a programmable RCR assembly strategy, our DNAzyme nanoplatform shows promise for developing smart gene therapeutics and personalized nanomedicines.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Analytical
Yu-Wen Zhang, Shan Li, Shu-Min Wang, Xiao-Qiong Li, Mei-Rong Cui, Bin Kang, Hong-Yuan Chen, Jing-Juan Xu
Summary: We developed a miRNA-responsive DNAzyme cascaded catalytic (MDCC) nanomachine for amplified intracellular miRNA imaging and miRNA-guided efficient gene silencing. The intelligent MDCC nanomachine consists of multiple DNAzyme subunit-encoded catalyzed hairpin assembly (CHA) reactants sustained by pH-responsive Zeolitic imidazolate framework-8 (ZIF-8) nanoparticles. Through a catalytic hairpin assembly (CHA) reaction triggered by the presence of miRNA-21, a large number of Y-shaped fluorescent DNA constructs containing three DNAzyme modules are generated for gene silencing. This strategy provides a promising platform for highly sensitive determination of biomolecules and accurate gene therapy of cancer cells.
Article
Biochemistry & Molecular Biology
Zhongchun Zhou, Wen Sun, Zhen Huang
Summary: Gene silencing is an important strategy for studying gene functions and diseases. 8-17 DNAzyme has high potential for gene silencing, but it is not widely used due to certain limitations. In this study, we explored its activity and found that it can cleave RNA substrates in simulated physiological conditions and its gene-silencing activity is enhanced by its compatibility with RNase H. Chemical modifications also improve its stability and gene-silencing activity. Our research suggests that this DNAzyme can be a useful tool for biomedical applications.
Article
Biochemistry & Molecular Biology
Jan Borggraefe, Christoph G. W. Gertzen, Aldino Viegas, Holger Gohlke, Manuel Etzkorn
Summary: Understanding the molecular features of catalytically active DNA sequences, known as DNAzymes, is crucial for comprehending their fundamental properties and unleashing their full potential through tailored modifications. Our recent research on the 10-23 DNAzyme has provided valuable insights into its unique molecular architecture, conformational plasticity, and dynamic modulation by metal ions, contributing to the exploration of DNA-mediated catalysis.
Article
Chemistry, Multidisciplinary
Yajun Wang, Kim Nguyen, Robert C. Spitale, John C. Chaput
Summary: Efforts to use RNA-cleaving DNA enzymes as gene-silencing agents have been hindered by low efficacy in clinical trials, but a new xeno-nucleic-acid-modified DNAzyme called X10-23 has shown promise in achieving multiple-turnover activity and resisting nuclease digestion in cellular conditions. X10-23 overcomes product inhibition and facilitates persistent gene silencing in mammalian cells, suggesting new molecular chemotypes can enhance the activity and stability of DNAzymes for potential therapeutic applications.
Article
Chemistry, Multidisciplinary
Huaixin Zhao, Zhili Zhang, Duo Zuo, Linghui Li, Feng Li, Dayong Yang
Summary: A DNA-polydopamine-MnO2 nanocomplex was developed for near-infrared light-powered catalytic activity of DNAzyme in vivo. The complex can enhance Egr-1 mRNA cleavage activity of DNAzyme, leading to downregulation of Egr-1 protein in tumor cells and achieving a synergistic tumor ablation effect through heat stress induction.
Article
Chemistry, Multidisciplinary
Evan R. R. Cramer, Sarah A. A. Starcovic, Rebekah M. M. Avey, Ali I. I. Kaya, Aaron R. R. Robart
Summary: Deoxyribozymes (DNAzymes) are evolved DNA sequences capable of catalyzing chemical reactions in vitro. The RNA-cleaving 10-23 DNAzyme, the first DNAzyme to be evolved, has important applications in clinical and biotechnology as a biosensor and a knockdown agent. Despite its advantages over other knockdown methods, such as siRNA and CRISPR, there is a lack of understanding of its structure and mechanism, limiting its optimization and application.
COMMUNICATIONS CHEMISTRY
(2023)
Review
Developmental Biology
Andrew Keniry, Marnie E. Blewitt
Summary: This article discusses the silencing process of the second X chromosome in females in mammals, and the crucial role of chromatin features in establishing and maintaining the silent state. It also explores the possibility of learning from this process to potentially treat X-linked diseases in females.
Article
Biochemistry & Molecular Biology
Huanhuan Liu, Yang Li, Shanshan Du, Chenhong Wang, Yuexiang Li, Ruiyuan Cao, Weiguo Shi, Shihui Liu, Junlin He
Summary: Cationic polymeric materials and cell-penetrating peptides were evaluated as delivery vectors for nucleic acid therapeutics. The effect of Lipofectamine 2000 and Tat peptide on the catalytic activity of 10-23 DNAzyme was assessed using rate constant, thermal stability, CD spectra, and PAGE analysis, with a duplex DNA mimicking DNAzyme-substrate as a control. It was found that the cationic carriers had a negative impact on the catalytic performance of 10-23 DNAzyme, particularly in destabilizing duplex formation, which is essential for the mechanisms of antisense and RNAi silencing.
Article
Cell Biology
Chen-Hua Dong, Tao Jiang, Hang Yin, Hu Song, Yi Zhang, Hao Geng, Pei-Cong Shi, Yi-Xin Xu, Hong Gao, Lian-Yu Liu, Lei Zhou, Zhao-Hui Zhang, Jun Song
Summary: LMNB2 is significantly upregulated in colorectal cancer tissues and cell lines, promoting cell proliferation by regulating cell cycle progression. It affects patient survival and may serve as a potential prognostic marker and therapy target by regulating p21-mediated mechanisms.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Omer Karin, Eric A. Miska, Benjamin D. Simons
Summary: Biological systems can maintain memories over long timescales, such as memories in the brain and immune system. This study focuses on transgenerational epigenetic inheritance in Caenorhabditis elegans to understand how functional properties of memory systems are established by biological circuits. The findings suggest that fine-tuning of biochemical rates and competition for synthesis resources play a role in maintaining memory persistence and self-organization around critical states.
Article
Biophysics
Yanmei Zhou, Wenxiao Ma, Ruijiao Sun, Bo Liu, Xiaoru Zhang, Hongsheng Yang
Summary: In this study, a nanodevice for intracellular miRNA detection and controlled drug release was developed based on upconverting nanoparticles (UCNPs). The device showed high sensitivity in miRNA-21 detection and allowed in situ diagnoses of miRNA-21 expression in living cells. Additionally, the integration of UCNPs with photocleavable linkers (PC-linkers) enabled artificially controlled chemo-gene synergetic therapy. The prepared nanodevice demonstrated potential application in cancer theranostics through in vitro and in vivo experiments.
BIOSENSORS & BIOELECTRONICS
(2022)
Article
Virology
Anshuman Das, Madhuvanthi Vijayan, Eric M. Walton, V. Grace Stafford, David N. Fiflis, Aravind Asokan
Summary: This study provides evidence that the double-stranded DNA binding protein NP220, in association with the human silencing hub (HUSH) complex, mediates transcriptional silencing of single-stranded as well as self-comple- mentary rAAV genomes. The AAV capsid appears to play an important role in NP220-mediated silencing of packaged genomes. Modulation of epigenetic pathways could potentially improve rAAV expression.
JOURNAL OF VIROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Xinyu Li, Mengxia Chen, Biru Liu, Peifen Lu, Xiang Lv, Xiang Zhao, Shuaiying Cui, Peipei Xu, Yukio Nakamura, Ryo Kurita, Bing Chen, David C. S. Huang, De-Pei Liu, Ming Liu, Quan Zhao
Summary: This study identified NonO as a novel transcriptional repressor of gamma-globin gene expression in human erythroid cells, through direct binding to the promoter. Depletion of NonO led to significant activation of gamma-globin expression. Further research also revealed a conserved role for NonO during mammalian evolution.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biology
James Attwater, Aditya Raguram, Alexey S. Morgunov, Edoardo Gianni, Philipp Holliger
Article
Biology
Hannes Mutschler, Alexander Taylor, Benjamin T. Porebski, Alice Lightowlers, Gillian Houlihan, Mikhail Abramov, Piet Herdewijn, Philipp Holliger
Article
Chemistry, Multidisciplinary
Sebastian Arangundy-Franklin, Alexander I. Taylor, Benjamin T. Porebski, Vito Genna, Sew Peak-Chew, Alexandra Vaisman, Roger Woodgate, Modesto Orozco, Philipp Holliger
Article
Chemistry, Multidisciplinary
Gillian Houlihan, Sebastian Arangundy-Franklin, Benjamin T. Porebski, Nithya Subramanian, Alexander I. Taylor, Philipp Holliger
Article
Biochemistry & Molecular Biology
Camille Samson, Pierre Legrand, Mustafa Tekpinar, Jef Rozenski, Mikhail Abramov, Philipp Holliger, Vitor B. Pinheiro, Piet Herdewijn, Marc Delarue
Article
Biochemistry & Molecular Biology
Thomas W. Christy, Catherine A. Giannetti, Gillian Houlihan, Matthew J. Smola, Greggory M. Rice, Jian Wang, Nikolay Dokholyan, Alain Laederach, Philipp Holliger, Kevin M. Weeks
Summary: The SHAPE-JuMP technique utilizes chemical reactions and engineered reverse transcriptase to rapidly and accurately reveal the three-dimensional interactions of large RNA molecules in solution, particularly effective for measuring interactions in multihelix junctions and loop-to-helix packing, enabling easier global folding modeling and structural model ranking.
Article
Biology
Emil Laust Kristoffersen, Matthew Burman, Agnes Noy, Philipp Holliger
Summary: RNA-catalyzed RNA replication is a crucial step in the emergence of life's first genetic system. This study explores rolling circle synthesis as a potential solution to the problem of strand separation. The results demonstrate that RNA can catalyze all steps of viroid-like RNA replication, and molecular dynamics simulations provide insights into the potential mechanism of rolling circle synthesis.
Review
Biochemical Research Methods
Niklas Freund, Maximilian Josef Ludwig Johannes Furst, Philipp Holliger
Summary: Nucleic acid chemistry has led to modifications of DNA and RNA structures, creating xeno-nucleic acids (XNAs) that are not naturally found and can be used in synthetic genetics for encoded synthesis, reverse transcription, and evolution.
CURRENT OPINION IN BIOTECHNOLOGY
(2022)
Article
Multidisciplinary Sciences
Peiying Li, Philipp Holliger, Shunsuke Tagami
Summary: Macromolecular aggregates are believed to have played a crucial role in the origin of life. This study reveals that hydrophobic-cationic peptides can form insoluble aggregates that reversibly bind to RNA and enhance RNA polymerization, suggesting their potential contribution to the emergence and evolution of longer, functional RNAs in the early Earth.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Alexander Taylor, Christopher J. K. Wan, Maria J. Donde, Sew-Yeu Peak-Chew, Philipp Holliger
Summary: This study reports the development of a highly specific RNA endonuclease XNAzyme, FR6_1, that can cleave highly structured full-length mRNA with allelic selectivity for tumor-associated mutations. This research provides a starting point for the development of improved gene-silencing agents based on FANA or other XNA chemistries.
Article
Chemistry, Multidisciplinary
Niklas Freund, Alexander Taylor, Sebastian Arangundy-Franklin, Nithya Subramanian, Sew-Yeu Peak-Chew, Amy M. Whitaker, Bret D. Freudenthal, Mikhail Abramov, Piet Herdewijn, Philipp Holliger
Summary: In this study, a two-residue "gate" was discovered in an archaeal DNA polymerase, which enables the synthesis of 2'-modified RNA oligomers. This discovery expands the application potential of 2'-modified RNA in nucleic acid therapeutics and biotechnology.
Article
Biochemistry & Molecular Biology
Peter Schofield, Alexander Taylor, Jerome Rihon, Cristian D. Pena Martinez, Sacha Zinn, Charles-Alexandre Mattelaer, Jennifer Jackson, Gurpreet Dhaliwal, Guy Schepers, Piet Herdewijn, Eveline Lescrinier, Daniel Christ, Philipp Holliger
Summary: Nucleic acids serve as the basis of heredity and are increasingly utilized to create novel nanostructures, devices, and drugs. Chemically modified alternatives, known as xeno nucleic acids (XNAs), have been developed to expand their chemical and functional capabilities. XNA aptamers, which can bind targets with high affinity and specificity, have not been thoroughly investigated in terms of their structure and function.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Falk Wachowius, Benjamin T. Porebski, Christopher M. Johnson, Philipp Holliger
Summary: We demonstrate that diverse sequence pools are not necessary for the emergence of function. By starting with a single RNA seed sequence and subjecting it to mutation, truncation, and recombination, we observe the transformation of the seed into a low diversity sequence pool. Through continuous error-prone replication and selection, we are able to isolate specific ATP- or GTP-binding aptamers with low micromolar affinities. These findings have significant implications for the understanding of early RNA evolution.
Article
Biochemistry & Molecular Biology
John R. D. Hervey, Niklas Freund, Gillian Houlihan, Gurpreet Dhaliwal, Philipp Holliger, Alexander Taylor
Summary: In this study, a method for the efficient synthesis and reverse transcription of libraries entirely composed of serum nuclease resistant alternative nucleic acid chemistries was described. The researchers found that besides pure 2'-O-methyl-RNA and LNA, several 2' OMe-RNA/LNA blends were suitable for the discovery of stable functional nucleic acids with biomedical applications.
RSC CHEMICAL BIOLOGY
(2022)
