Article
Biochemistry & Molecular Biology
David Kutak, Lucas Melo, Fabian Schroeder, Zoe Jelic-Matosevic, Natalie Mutter, Branimir Bertosa, Ivan Barisic
Summary: Significant advances have been made in the rational design of proteins, DNA, and other organic nanostructures in the last decade. The ability to engineer molecular structures precisely has resulted in a wide range of applications in fields such as biotechnology and medicine. However, the increasing complexity and size of artificial molecular systems require computational design support. This study presents Catana, a web-based modelling environment for proteins and DNA nanostructures, which allows users to create and modify recombinant fusion proteins, predict protein structures, and manipulate DNA origami structures.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Nanoscience & Nanotechnology
Klaus F. Wagenbauer, Nhi Pham, Adrian Gottschlich, Benjamin Kick, Viktorija Kozina, Christopher Frank, Daniela Trninic, Pierre Stoemmer, Ruth Gruenmeier, Emanuele Carlini, Christina Angeliki Tsiverioti, Sebastian Kobold, Jonas J. Funke, Hendrik Dietz
Summary: A synthetic nanocarrier based on DNA origami chassis allows for precise control of antibodies in anticancer immunotherapy, enabling simultaneous engagement with immune signalling pathways, checkpoint inhibition, and targeted co-stimulation. Through modular and programmable assembly, specific T-cell engagers were identified and tested for their ability to activate T cells and induce lysis of target cells, both in vitro and in vivo. This approach provides a rapid and efficient method for the generation, screening, and testing of multi-specific antibodies in preclinical pharmaceutical development.
NATURE NANOTECHNOLOGY
(2023)
Article
Chemistry, Physical
Shaoli Liu, Qiao Jiang, Xiao Zhao, Ruifang Zhao, Yuanning Wang, Yiming Wang, Jianbing Liu, Yingxu Shang, Shuai Zhao, Tiantian Wu, Yinlong Zhang, Guangjun Nie, Baoquan Ding
Summary: A DNA nanodevice vaccine has been developed to stimulate a tumor-specific cytotoxic T lymphocyte response, leading to inhibition of tumor growth and prevention of metastasis. The vaccine utilizes molecular adjuvants and antigen peptides within a tubular DNA nanostructure to trigger T-cell activation and cancer cytotoxicity, showing promising results in mouse cancer models. The vaccination generates long-term T-cell responses which effectively protect against tumor rechallenge.
Article
Multidisciplinary Sciences
Chunyang Zhou, Donglei Yang, Sebastian Sensale, Pranav Sharma, Dongfang Wang, Lei Yu, Gaurav Arya, Yonggang Ke, Pengfei Wang
Summary: This study reports a design method for controllable DNA molecular structures through controlled base stacking. Precise control over molecular conformation and transformation is achieved by programming stacking bonds within the junction. Dynamic transformations between different conformations are achieved through specific environmental and molecular stimulations.
Article
Multidisciplinary Sciences
Daniel Fu, Raghu Pradeep Narayanan, Abhay Prasad, Fei Zhang, Dewight Williams, John S. Schreck, Hao Yan, John Reif
Summary: We have developed an automated design tool that can be applied to curved geometries for encapsulating three-dimensional DNA nanostructures. This research is significant in solving previous design challenges and expanding the application of DNA nanostructure design.
Article
Nanoscience & Nanotechnology
Christopher M. M. Wintersinger, Dionis Minev, Anastasia Ershova, Hiroshi M. M. Sasaki, Gokul Gowri, Jonathan F. F. Berengut, F. Eduardo Corea-Dilbert, Peng Yin, William M. M. Shih
Summary: Living systems can self-assemble at different length scales, and DNA origami techniques have enabled the self-assembly of submicron-scale shapes. By extending the crisscross polymerization strategy to DNA origami slats, custom multi-micron shapes with nanoscale surface patterning can be fabricated. This method allows for the production of complex structures composed of thousands of sophisticated and precisely designed origami slats.
NATURE NANOTECHNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Yan Li, Jin Pei, Xuehe Lu, Yunfei Jiao, Fengsong Liu, Xiaohui Wu, Jianbing Liu, Baoquan Ding
Summary: The DNA origami technique offers a programmable way to assemble nanostructures with arbitrary shapes, limited only by the scaffold strand length. A new strategy has been developed to efficiently organize multiple DNA origami tiles into super-DNA origami using a flexible and covalent-bound branched DNA structure. Compared to traditional DNA junctions, this approach yields higher efficiency and more compact structures, enabling precise organization of gold nanoparticles into various patterns.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Jing Yang, Yuan Liang, Xiang Li, Yongpeng Zhang, Long Qian, Yonggang Ke, Cheng Zhang
Summary: The programmable assembly of gold nanoparticle superstructures with precise spatial arrangement has attracted attention for their unique characteristics in plasmonics and biomedicine. This article presents a strategy of using a spatially programmable enzymatic nanorobot arm to modulate the anisotropic assembly of DNA/AuNP superstructures.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Bo-Young Lee, Jaewon Lee, Dong June Ahn, Seungwoo Lee, Min-Kyu Oh
Summary: Reducing the expression of phage protein V was found to significantly enhance the production throughput of scaffold DNA. Reprogramming rolling circle amplification in Escherichia coli can lead to a substantial improvement in scaffold DNA production efficiency.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Wouter Engelen, Christian Sigl, Karoline Kadletz, Elena M. Willner, Hendrik Dietz
Summary: This study presents a strategy for controlling DNA nanodevices based on IgG antibodies sensing antigens, allowing for antigen-triggered disassembly and release of molecular payload. The method is applicable in various DNA nanostructures and IgG-antigen combinations.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Enrique Lin-Shiao, Wolfgang G. Pfeifer, Brian R. Shy, Mohammad Saffari Doost, Evelyn Chen, Vivasvan S. Vykunta, Jennifer R. Hamilton, Elizabeth C. Stahl, Diana M. Lopez, Cindy R. Sandoval Espinoza, Alexander E. Deyanov, Rachel J. Lew, Michael G. Poirer, Alexander Marson, Carlos E. Castro, Jennifer A. Doudna
Summary: DNA nanostructures are a promising tool for delivering molecular payloads to cells, but effectively delivering genetic material to the nucleus has been a challenge. This study successfully integrated gene material into cells using DNA nanostructures as HDR templates, with increased entry into the nucleus through CRISPR technology. These nanostructured templates showed lower toxicity and higher insertion efficiency compared to unstructured DNA templates.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Katsuhiko Abe, Hiroshi Sugiyama, Masayuki Endo
Summary: The study demonstrates photo-controlled sequence-selective dsDNA cleavage using a DNA origami structure with Cas9 nuclease. The activity of Cas9 was suppressed inside the ring-shaped DNA origami and restored after photoirradiation.
CHEMICAL COMMUNICATIONS
(2021)
Article
Robotics
Namita Sarraf, Kellen R. Rodriguez, Lulu Qian
Summary: The power of natural evolution lies in the adaptability of biological organisms, but it is limited by the time scale of genetics and reproduction. Engineering artificial molecular machines that have adaptability as a core feature and operate at a faster time scale could revolutionize synthetic cells. We developed a tile displacement mechanism in DNA origami assemblies to achieve modular reconfiguration, and we established design principles for simultaneous reconfigurations using complex invaders with distinct shapes.
Article
Multidisciplinary Sciences
Longfei Liu, Qiancheng Xiong, Chun Xie, Frederic Pincet, Chenxiang Lin
Summary: The triggered formation of membrane tubes in response to specific DNA signals allows for spatial and temporal control of membrane dynamics in an artificial system. The conformational change of DNA clamps can modulate the timing, efficiency, and width of vesicle tubulation.
Article
Biotechnology & Applied Microbiology
Amin Mirzaiebadizi, Hadi Ravan, Shahriar Dabiri, Pourya Mohammadi, Arezoo Shahba, Mahsa Ziasistani, Mehrdad Khatami
Summary: In this study, we designed an intelligent nanorobot based on a DNA framework for the selective and synchronous detection of miR21 and miR125b, which are significant cancer biomarkers. By using capping agents on mesoporous silica nanoparticles (MSNs), we achieved specific drug release in the presence of both targets. The results showed that this hybrid DNA nanostructure can respond to any target oligonucleotides with a length of 22 nucleotides.
BIOPROCESS AND BIOSYSTEMS ENGINEERING
(2022)
Article
Physics, Multidisciplinary
Florian Katzmeier, Bernhard Altaner, Jonathan List, Ulrich Gerland, Friedrich C. Simmel
Summary: Suspended microparticles can form stripe patterns perpendicular to the direction of an ac electrical field, which further develop into zigzag patterns. This phenomenon can be accurately simulated and predicted by second order electrokinetic flow, and can be observed with various types of particles.
PHYSICAL REVIEW LETTERS
(2022)
Article
Multidisciplinary Sciences
Aurore Dupin, Lukas Aufinger, Igor Styazhkin, Florian Rothfischer, Benedikt K. Kaufmann, Sascha Schwarz, Nikolas Galensowske, Hauke Clausen-Schaumann, Friedrich C. Simmel
Summary: Biomaterials composed of synthetic cells have the potential to adapt and differentiate based on physicochemical cues. This study investigates the ability of synthetic cells to determine their position within a multicellular structure, inspired by natural systems. The findings show that gene expression noise and the temporal evolution of the morphogen gradient and cell-free expression system affect the accuracy of positional information. Computational modeling can rationalize the generation of positional information. The approach is scaled up using three-dimensional printing and demonstrates morphogen-based differentiation in larger tissue-like assemblies.
Article
Multidisciplinary Sciences
Anna-Katharina Pumm, Wouter Engelen, Enzo Kopperger, Jonas Isensee, Matthias Vogt, Viktorija Kozina, Massimo Kube, Maximilian N. Honemann, Eva Bertosin, Martin Langecker, Ramin Golestanian, Friedrich C. Simmel, Hendrik Dietz
Summary: To achieve directional motion in a molecular mechanism, researchers have developed a method using Brownian ratchets that break inversion symmetry. Previous work in DNA nanotechnology has shown the possibility of constructing nanoscale mechanisms that can undergo different configurations and motions. Based on these findings, researchers have created a nanoscale rotary motor built from DNA origami that approaches the mechanical capabilities of biological motors.
Article
Chemistry, Multidisciplinary
Antti Elonen, Ashwin Karthick Natarajan, Ibuki Kawamata, Lukas Oesinghaus, Abdulmelik Mohammed, Jani Seitsonen, Yuki Suzuki, Friedrich C. Simmel, Anton Kuzyk, Pekka Orponen
Summary: This study presents an algorithmic design process and software pipeline for rendering 3D wireframe polyhedral nanostructures in single-stranded RNA. Users can create models of desired nanostructures using standard 3D graphic design software, and the pipeline generates corresponding RNA nucleotide sequences for experimental folding in the laboratory.
Article
Biophysics
Adrian Buchl, Enzo Kopperger, Matthias Vogt, Martin Langecker, Friedrich C. Simmel, Jonathan List
Summary: Biomolecular nanomechanical devices are used to process and manipulate molecules, and DNA nanotechnology can be used to build molecular structures similar to mechanical machine elements, improving performance and behavior.
BIOPHYSICAL JOURNAL
(2022)
Article
Biophysics
Yash Bogawat, Swati Krishnan, Friedrich C. Simmel, Ibon Santiago
Summary: This study used DNA nanotechnology to track the dynamics of DNA nanostructures on lipid bilayers in two dimensions. The diffusion coefficient of the nanostructures can be modulated by changing salt concentration and the number of anchors, as well as selectively displacing anchor strands.
BIOPHYSICAL JOURNAL
(2022)
News Item
Chemistry, Multidisciplinary
Jongmin Kim, Friedrich C. Simmel
Summary: DNA nanotechnology and synthetic biology aim to expand the range of dynamic behaviors exhibited by biomolecules. The programmability of synthetic transcriptional circuits has been improved to enable synthesis of dynamic biomolecular circuits with unmatched complexity.
Article
Biochemical Research Methods
Anna C. Jaekel, Lukas Aufinger, Friedrich C. Simmel
Summary: Pattern formation processes are crucial in embryogenesis and can be studied using synthetic gene circuits. In this study, a three-node feed-forward gene regulatory circuit was investigated, which responded to varying concentrations of a single morphogen by generating distinct fluorescent outputs. The importance of non-equilibrium operation for the correct functionality of complex gene circuits was emphasized.
ACS SYNTHETIC BIOLOGY
(2022)
Review
Materials Science, Biomaterials
Anna C. Jaekel, Michael Heymann, Friedrich C. Simmel
Summary: Structure and hierarchical organization are crucial for engineering synthetic biomaterials with life-like behavior. Additive manufacturing techniques like bioprinting show limited resolution, making it challenging to create sub-cellular level structures. Combining manufacturing techniques with biomolecular nanotechnology is necessary to create macroscopic synthetic biological objects with structuring on this level.
Review
Biochemical Research Methods
Tianhe Wang, Henning Hellmer, Friedrich C. Simmel
Summary: Toehold-mediated strand displacement (TMSD) is an isothermal switching process that allows the programmable and reversible conversion of DNA or RNA strands between different conformations. TMSD has been widely used in DNA nanotechnology for driving molecular devices and synthetic biochemical computing circuits. Recently, researchers have started using TMSD for controlling RNA-based gene regulation in vivo, particularly in the context of riboregulators and conditional guide RNAs for CRISPR/Cas. This review provides an overview of recent developments in this emerging field and discusses the opportunities and challenges for in vivo applications of TMSD.
CURRENT OPINION IN BIOTECHNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Thomas Mayer, Lukas Oesinghaus, Friedrich C. Simmel
Summary: We investigated the impact of random DNA sequences on TMSD circuits and found that only a small subpopulation of strongly interacting strands determined the kinetics. We also compared three techniques to speed up TMSD reactions and found that only the last one can be used without sequence constraints.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Alessandro Cecconello, Massimiliano Magro, Fabio Vianello, Friedrich C. Simmel
Summary: This study demonstrates the formation of triplex nanostructures in vitro in the promoter region of DNA templates, and proposes the possibility of regulating RNA transcription using these structures. Hybrid DNA-RNA triplex nanostructures were designed to have switchable promoters and enhance transcriptional activity. The results suggest that triplex forming RNA oligonucleotides could serve as smart tools for transcriptional modulation.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Physics, Multidisciplinary
Matthias Vogt, Martin Langecker, Matthias Gouder, Enzo Kopperger, Florian Rothfischer, Friedrich C. Simmel, Jonathan List
Summary: By winding up and relaxing a molecular joint, the mechanical energy can be stored and released to drive the rotation of a DNA nanodevice. Designing molecular machine elements that effectively power the connectivity of rigid structural components is a fundamental challenge in the field of DNA-based nanodevices and nanorobots. Through electrical manipulation and single molecule fluorescence microscopy, we study the mechanical properties of different joint designs, with simulations suggesting that breaking of stacking interactions plays a major role in enthalpic energy storage.
Review
Biochemistry & Molecular Biology
Friedrich C. Simmel
Summary: Nucleic acid strand displacement reactions involve the competition of similar DNA or RNA strands for binding, facilitating the replacement of an incumbent strand. By augmenting the incumbent duplex with a single-stranded extension, a toehold is provided for a complementary invader, giving it a thermodynamic advantage. Toehold-mediated strand displacement processes have been widely used in DNA-based molecular machines and gene regulatory switches.
Article
Biochemistry & Molecular Biology
Quirin Emslander, Kilian Vogele, Peter Braun, Jana Stender, Christian Willy, Markus Joppich, Jens A. Hammerl, Miriam Abele, Chen Meng, Andreas Pichlmair, Christina Ludwig, Joachim J. Bugert, Friedrich C. Simmel, Gil G. Westmeyer
Summary: Researchers have demonstrated a comprehensive cell-free platform for personalized production, transient engineering, and proteomic characterization of a broad spectrum of phages. They have also developed a non-genomic phage engineering method and successfully produced effective doses of phages against multiple bacteria. This study is important for phage engineering and customized production of clinical-grade bacteriophages.
CELL CHEMICAL BIOLOGY
(2022)