A Molecular Hero Suit for In Vitro and In Vivo DNA Nanostructures

Small ◽  
2019 ◽  
Vol 15 (26) ◽  
pp. 1805386 ◽  
Author(s):  
Megan E. Kizer ◽  
Robert J. Linhardt ◽  
Arun Richard Chandrasekaran ◽  
Xing Wang
Keyword(s):  
2021 ◽  
Author(s):  
Zenita Adhireksan ◽  
Deepti Sharma ◽  
Phoi Leng Lee ◽  
Qiuye Bao ◽  
Sivaraman Padavattan ◽  
...  

Abstract Structural characterization of chromatin is challenging due to conformational and compositional heterogeneity in vivo and dynamic properties that limit achievable resolution in vitro. Although the maximum resolution for solving structures of large macromolecular assemblies by electron microscopy has recently undergone profound increases, X-ray crystallographic approaches may still offer advantages for certain systems. One such system is compact chromatin, wherein the crystalline state recapitulates the crowded molecular environment within the nucleus. Here we show that nucleosomal constructs with cohesive-ended DNA can be designed that assemble into different types of circular configurations or continuous fibers extending throughout crystals. We demonstrate the utility of the method for characterizing nucleosome compaction and linker histone binding at near-atomic resolution but also advance its application for tackling further problems in chromatin structural biology and for generating novel types of DNA nanostructures. We provide a library of cohesive-ended DNA fragment expression constructs and a strategy for engineering DNA-based nanomaterials with a seemingly vast potential variety of architectures and histone chemistries.


2018 ◽  
Vol 114 (3) ◽  
pp. 693a ◽  
Author(s):  
Christina Kolonelou ◽  
Alessandro Bosco ◽  
Björn Högberg ◽  
Ana Teixeira

2017 ◽  
Vol 106 (9) ◽  
pp. 2457-2462 ◽  
Author(s):  
Yosuke Takahashi ◽  
Tatsuoki Maezawa ◽  
Yuki Araie ◽  
Yuki Takahashi ◽  
Yoshinobu Takakura ◽  
...  

Small ◽  
2019 ◽  
Vol 15 (26) ◽  
pp. 1970141
Author(s):  
Megan E. Kizer ◽  
Robert J. Linhardt ◽  
Arun Richard Chandrasekaran ◽  
Xing Wang
Keyword(s):  

2008 ◽  
Vol 105 (46) ◽  
pp. 17626-17631 ◽  
Author(s):  
Chenxiang Lin ◽  
Sherri Rinker ◽  
Xing Wang ◽  
Yan Liu ◽  
Nadrian C. Seeman ◽  
...  

Mimicking nature is both a key goal and a difficult challenge for the scientific enterprise. DNA, well known as the genetic-information carrier in nature, can be replicated efficiently in living cells. Today, despite the dramatic evolution of DNA nanotechnology, a versatile method that replicates artificial DNA nanostructures with complex secondary structures remains an appealing target. Previous success in replicating DNA nanostructures enzymatically in vitro suggests that a possible solution could be cloning these nanostructures by using viruses. Here, we report a system where a single-stranded DNA nanostructure (Holliday junction or paranemic cross-over DNA) is inserted into a phagemid, transformed into XL1-Blue cells and amplified in vivo in the presence of helper phages. High copy numbers of cloned nanostructures can be obtained readily by using standard molecular biology techniques. Correct replication is verified by a number of assays including nondenaturing PAGE, Ferguson analysis, endonuclease VII digestion, and hydroxyl radical autofootprinting. The simplicity, efficiency, and fidelity of nature are fully reflected in this system. UV-induced psoralen cross-linking is used to probe the secondary structure of the inserted junction in infected cells. Our data suggest the possible formation of the immobile four-arm junction in vivo.


2020 ◽  
Author(s):  
Shai Zilberzwige-Tal ◽  
Dan Alon ◽  
Danielle Gazit ◽  
Shahar Zachariah ◽  
Amit Hollander ◽  
...  

Abstract DNA nanotechnology is leading the field of in vitro molecular-scale device engineering, accumulating to a dazzling array of applications from zeolite-like catalysts to bio-imaging. However, while DNA nanostructures' function is robust under in vitro settings, their implementation in real-world conditions requires overcoming their rapid degradation and subsequent loss of function. Viruses are incredibly sophisticated supramolecular assemblies, able to protect their nucleic acid content in the relatively inhospitable biological environment. Inspired by this natural ability, we engineered both in vitro and in vivo technologies, enabling the encapsulation and protection of functional DNA nanostructures inside MS2 bacteriophage virus-like particles (VLPs). We demonstrate the ssDNA-VLPs nanocomposites (NCs) abilities to encapsulate single-stranded-DNA (ssDNA) of an unprecedented variety of sizes (200–1500 nucleotides (nt)), sequences, and structures while retaining their functionality. Moreover, by exposing these NCs to hostile biological conditions, such as human blood serum, we exhibit that the VLPs serves as an excellent protective shell. To the best of our knowledge, these engineered NCs pose key properties that are yet unattainable by current fabrication methods.


Nano Today ◽  
2019 ◽  
Vol 26 ◽  
pp. 98-107 ◽  
Author(s):  
Wooli Bae ◽  
Samet Kocabey ◽  
Tim Liedl
Keyword(s):  

2020 ◽  
Vol 4 (6) ◽  
pp. 555-566
Author(s):  
Ioanna Mela ◽  
Clemens F. Kaminski

Antibiotic resistance has become one of the greatest challenges for modern medicine, and new approaches for the treatment of bacterial infections are urgently needed to avoid widespread vulnerability again to infections that have so far been easily treatable with existing drugs. Among the many approaches investigated to overcome this challenge is the use of engineered nanostructures for the precise and targeted delivery of existing antimicrobial agents in a fashion that will potentiate their effect. This idea leans on lessons learned from pioneering research in cancer, where the targeted delivery of anti-cancer drugs to mammalian cells has been a topic for some time. In particular, new research has demonstrated that nanomaterials can be functionalised with active antimicrobials and, in some cases, with targeting molecules that potentiate the efficiency of the antimicrobials. In this mini-review, we summarise results that demonstrate the potential for nanoparticles, dendrimers and DNA nanostructures for use in antimicrobial delivery. We consider material aspects of the delivery vehicles and ways in which they can be functionalised with antibiotics and antimicrobial peptides, and we review evidence for their efficacy to kill bacteria both in vitro and in vivo. We also discuss the advantages and limitations of these materials and highlight the benefits of DNA nanostructures specifically for their versatile potential in the present context.


Author(s):  
E. J. Kollar

The differentiation and maintenance of many specialized epithelial structures are dependent on the underlying connective tissue stroma and on an intact basal lamina. These requirements are especially stringent in the development and maintenance of the skin and oral mucosa. The keratinization patterns of thin or thick cornified layers as well as the appearance of specialized functional derivatives such as hair and teeth can be correlated with the specific source of stroma which supports these differentiated expressions.


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