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1. Rationally Programming Nanomaterials with DNA for Biomedical Applications

   https://doi.org/10.1002/advs.202003775  

   He, Liangcan; Mu, Jing; Gang, Oleg; Chen, Xiaoyuan (February 2021, Advanced Science)

   Abstract DNA is not only a carrier of genetic information, but also a versatile structural tool for the engineering and self‐assembling of nanostructures. In this regard, the DNA template has dramatically enhanced the scalability, programmability, and functionality of the self‐assembled DNA nanostructures. These capabilities provide opportunities for a wide range of biomedical applications in biosensing, bioimaging, drug delivery, and disease therapy. In this review, the importance and advantages of DNA for programming and fabricating of DNA nanostructures are first highlighted. The recent progress in design and construction of DNA nanostructures are then summarized, including DNA conjugated nanoparticle systems, DNA‐based clusters and extended organizations, and DNA origami‐templated assemblies. An overview on biomedical applications of the self‐assembled DNA nanostructures is provided. Finally, the conclusion and perspectives on the self‐assembled DNA nanostructures are presented. 

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2. Assembly of Two‐Dimensional DNA Arrays Could Influence the Formation of Their Component Tiles

   https://doi.org/10.1002/cbic.202200306  

   Paluzzi, Victoria E.; Zhang, Cuizheng; Mao, Chengde (July 2022, ChemBioChem)

   Abstract Tile‐based DNA self‐assembly is a powerful approach for nano‐constructions. In this approach, individual DNA single strands first assemble into well‐defined structural tiles, which, then, further associate with each other into final nanostructures. It is a general assumption that the lower‐level structures (tiles) determine the higher‐level, final structures. In this study, we present concrete experimental data to show that higher‐level structures could, at least in the current example, also impact on the formation of lower‐level structures. This study prompts questions such as: how general is this phenomenon in programmed DNA self‐assembly and can we turn it into a useful tool for fine tuning DNA self‐assembly? 

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3. CRISPR–Cas9-mediated nuclear transport and genomic integration of nanostructured genes in human primary cells

   https://doi.org/10.1093/nar/gkac049  

   Lin-Shiao, Enrique; Pfeifer, Wolfgang G.; Shy, Brian R.; Saffari Doost, Mohammad; Chen, Evelyn; Vykunta, Vivasvan S.; Hamilton, Jennifer R.; Stahl, Elizabeth C.; Lopez, Diana M.; Sandoval Espinoza, Cindy R.; et al (February 2022, Nucleic Acids Research)

   Abstract DNA nanostructures are a promising tool to deliver molecular payloads to cells. DNA origami structures, where long single-stranded DNA is folded into a compact nanostructure, present an attractive approach to package genes; however, effective delivery of genetic material into cell nuclei has remained a critical challenge. Here, we describe the use of DNA nanostructures encoding an intact human gene and a fluorescent protein encoding gene as compact templates for gene integration by CRISPR-mediated homology-directed repair (HDR). Our design includes CRISPR–Cas9 ribonucleoprotein binding sites on DNA nanostructures to increase shuttling into the nucleus. We demonstrate efficient shuttling and genomic integration of DNA nanostructures using transfection and electroporation. These nanostructured templates display lower toxicity and higher insertion efficiency compared to unstructured double-stranded DNA templates in human primary cells. Furthermore, our study validates virus-like particles as an efficient method of DNA nanostructure delivery, opening the possibility of delivering nanostructures in vivo to specific cell types. Together, these results provide new approaches to gene delivery with DNA nanostructures and establish their use as HDR templates, exploiting both their design features and their ability to encode genetic information. This work also opens a door to translate other DNA nanodevice functions, such as biosensing, into cell nuclei. 

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4. DNAcycP: a deep learning tool for DNA cyclizability prediction

   https://doi.org/10.1093/nar/gkac162  

   Li, Keren; Carroll, Matthew; Vafabakhsh, Reza; Wang, Xiaozhong A.; Wang, Ji-Ping (March 2022, Nucleic Acids Research)

   Abstract DNA mechanical properties play a critical role in every aspect of DNA-dependent biological processes. Recently a high throughput assay named loop-seq has been developed to quantify the intrinsic bendability of a massive number of DNA fragments simultaneously. Using the loop-seq data, we develop a software tool, DNAcycP, based on a deep-learning approach for intrinsic DNA cyclizability prediction. We demonstrate DNAcycP predicts intrinsic DNA cyclizability with high fidelity compared to the experimental data. Using an independent dataset from in vitro selection for enrichment of loopable sequences, we further verified the predicted cyclizability score, termed C-score, can well distinguish DNA fragments with different loopability. We applied DNAcycP to multiple species and compared the C-scores with available high-resolution chemical nucleosome maps. Our analyses showed that both yeast and mouse genomes share a conserved feature of high DNA bendability spanning nucleosome dyads. Additionally, we extended our analysis to transcription factor binding sites and surprisingly found that the cyclizability is substantially elevated at CTCF binding sites in the mouse genome. We further demonstrate this distinct mechanical property is conserved across mammalian species and is inherent to CTCF binding DNA motif. 

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5. DNA Functionality with Photoswitchable Hydrazone Cytidine**

   https://doi.org/10.1002/chem.202100742  

   Mao, Song; Chang, Zhihua; Ying Zheng, Ya; Shekhtman, Alexander; Sheng, Jia (May 2021, Chemistry – A European Journal)

   Abstract A new family of hydrazone modified cytidine phosphoramidite building block was synthesized and incorporated into oligodeoxynucleotides to construct photoswitchable DNA strands. TheE‐Zisomerization triggered by the irradiation of blue light with a wavelength of 450 nm was investigated and confirmed by¹H NMR spectroscopy and HPLC in the contexts of both nucleoside and oligodeoxynucleotide. The light activatedZform isomer of this hydrazone‐cytidine with a six‐member intramolecular hydrogen bond was found to inhibit DNA synthesis in the primer extension model by usingBstDNA polymerase. In addition, the hydrazone modification caused the misincorporation of dATP together with dGTP into the growing DNA strand with similar selectivity, highlighting a potential G to A mutation. This work provides a novel functional DNA building block and an additional molecular tool that has potential chemical biology and biomedicinal applications to control DNA synthesis and DNA‐enzyme interactions using the cell friendly blue light irradiation. 

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