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  1. Abstract

    Access to fast and reliable nucleic acid testing continues to play a key role in controlling the COVID-19 pandemic, especially in the context of increased vaccine break-through risks due to new variants. We report a rapid, low-cost (~ 2 USD), simple-to-use nucleic acid test kit for self-administered at-home testing without lab instrumentation. The entire sample-to-answer workflow takes < 60 min, including noninvasive sample collection, one-step RNA preparation, reverse-transcription loop-mediated isothermal amplification (RT-LAMP) in a thermos, and direct visual inspection of a colorimetric test result. To facilitate long-term storage without cold-chain, a fast one-pot lyophilization protocol was developed to preserve all required biochemical reagents of the colorimetric RT-LAMP test in a single microtube. Notably, the lyophilized RT-LAMP assay demonstrated reduced false positives as well as enhanced tolerance to a wider range of incubation temperatures compared to solution-based RT-LAMP reactions. We validated our RT-LAMP assay using simulated infected samples, and detected a panel of SARS-CoV-2 variants with successful detection of all variants that were available to us at the time. With a simple change of the primer set, our lyophilized RT-LAMP home test can be easily adapted as a low-cost surveillance platform for other pathogens and infectious diseases of global public health importance.

     
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  2. DNA computing has emerged as a promising alternative to achieve programmable behaviors in chemistry by repurposing the nucleic acid molecules into chemical hardware upon which synthetic chemical programs can be executed. These chemical programs are capable of simulating diverse behaviors, including boolean logic computation, oscillations, and nanorobotics. Chemical environments such as the cell are marked by uncertainty and are prone to random fluctuations. For this reason, potential DNA-based molecular devices that aim to be deployed into such environments should be capable of adapting to the stochasticity inherent in them. In keeping with this goal, a new subfield has emerged within DNA computing, focusing on developing approaches that embed learning and inference into chemical reaction systems. If realized in biochemical contexts, such molecular machines can engender novel applications in fields such as biotechnology, synthetic biology, and medicine. Therefore, it would be beneficial to review how different ideas were conceived, how the progress has been so far, and what the emerging ideas are in this nascent field of ‘molecular-scale learning’. 
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    Free, publicly-accessible full text available May 4, 2024
  3. Heuristic algorithms can generalize the design process of stiff and round capsule-like nanostructures made from DNA. 
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  4. Structural DNA nanotechnology is a pioneering biotechnology that presents the opportunity to engineer DNA-based hardware that will mediate a profound interface to the nanoscale. To date, an enormous library of shaped 3D DNA nanostructures have been designed and assembled. Moreover, recent research has demonstrated DNA nanostructures that are not only static but can exhibit specific dynamic motion. DNA nanostructures have thus garnered significant research interest as a template for pursuing shape and motion-dependent nanoscale phenomena. Potential applications have been explored in many interdisciplinary areas spanning medicine, biosensing, nanofabrication, plasmonics, single-molecule chemistry, and facilitating biophysical studies. In this review, we begin with a brief overview of general and versatile design techniques for 3D DNA nanostructures as well as some techniques and studies that have focused on improving the stability of DNA nanostructures in diverse environments, which is pivotal for its reliable utilization in downstream applications. Our main focus will be to compile a wide body of existing research on applications of 3D DNA nanostructures that demonstrably rely on the versatility of their mechanical design. Furthermore, we frame reviewed applications into three primary categories, namely encapsulation, surface templating, and nanomechanics, that we propose to be archetypal shape- or motion-related functions of DNA nanostructures found in nanoscience applications. Our intent is to identify core concepts that may define and motivate specific directions of progress in this field as we conclude the review with some perspectives on the future. 
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