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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. Beyond a few bases: methods for large DNA insertion and gene targeting in plants

   https://doi.org/10.1111/tpj.70099  

   Vollen, Katie; Alonso, Jose_M; Stepanova, Anna_N (March 2025, The Plant Journal)

   SUMMARY Genome editing technologies like CRISPR/Cas have greatly accelerated the pace of both fundamental research and translational applications in agriculture. However, many plant biologists are functionally limited to creating small, targeted DNA changes or large, random DNA insertions. The ability to efficiently generate large, yet precise, DNA changes will massively accelerate crop breeding cycles, enabling researchers to more efficiently engineer crops amidst a rapidly changing agricultural landscape. This review provides an overview of existing technologies that allow plant biologists to integrate large DNA sequences within a plant host and some associated technical bottlenecks. Additionally, this review explores a selection of emerging techniques in other host systems to inspire tool development in plants. 

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3. Single‐Particle Tracking Microelectrophoresis Analysis of Charge and Cargo Loading on Gene Delivery Microbubbles

   https://doi.org/10.1002/ppsc.202400187  

   Huynh, Katherine T; Armstrong, Randall; Speese, Sean; Schutt, Carolyn E (April 2025, Particle & Particle Systems Characterization)

   Abstract Lipid‐coated microbubbles are an important class of gene delivery vehicles activated by ultrasound to locally deliver their DNA payloads to cells. Negatively charged DNA is electrostatically loaded onto the positively charged surface of microbubbles that contain a cationic lipid shell. Characterizing the zeta potential of individual cationic microbubbles to determine a population distribution and how this is affected by DNA complexation is critical to maximize DNA loading and circulation time. Traditional zeta potential analysis provides an ensemble charge measurement for a particle population but cannot measure individual particles to determine a distribution. Here, single‐particle tracking microelectrophoresis technology is applied to measure zeta potentials of individual microbubbles synthesized with different ratios of 1,2‐distearoyl‐3‐trimethylammonium‐propane (DSTAP) cationic lipid as well as loaded with increasing amounts of DNA. Results show that at 0 mol% DSTAP all microbubbles are negatively charged, and at 10 mol% half are positive. All particles are positive at 20 mol% DSTAP but the population shifts to negative values upon incubation with 0.01 pg DNA/microbubble. Analyzing zeta potential on the individual microbubble level is a powerful tool to understand DNA loading across a population of microbubbles and enables microbubble surface charge and nucleic acid loading optimization for delivery applications. 

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4. 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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5. Generative design-enabled exploration of wireframe DNA origami nanostructures

   https://doi.org/10.1093/nar/gkae1268  

   Vetturini, Anthony J.; Cagan, Jonathan; Taylor, Rebecca E. (December 2024, Nucleic Acids Research)

   Abstract Recent advances in computer-aided design tools have helped rapidly advance the development of wireframe DNA origami nanostructures. Specifically, automated tools now exist that can convert an input polyhedral mesh into a DNA origami nanostructure, greatly reducing the design difficulty for wireframe DNA origami nanostructures. However, one limitation of these automated tools is that they require a designer to fully conceptualize their intended nanostructure, which may be limited by their own preconceptions. Here, a generative design framework is introduced capable of generating many wireframe DNA origami nanostructures without the need for a predefined mesh. User-defined objectives that guide the generative process are input as either single- or multi-objective optimization problems. A graph grammar is used to both contextualize physical properties of the DNA nanostructure and control the types of generated design features. This framework allows a designer to explore upon and ideate among many generated nanostructures that comply with their own unique constraints. A web-based graphical user interface is provided, allowing users to compare various generated solutions side by side in an interactive environment. Overall, this work illustrates how a constrained generative design framework can be implemented as an assistive tool in exploring design-feature trade-offs of wireframe DNA nanostructures, resulting in novel wireframe nanostructures. 

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