Using DNA origami as the recognition element in an electrochemical biosensor enables the selective and direct detection of “mesoscale” virus-sized analytes.
It has been demonstrated that microRNA-122 (miR-122) plays key roles in the modulation of hepatitis B virus (HBV) replication. This study examined the role of miR-122 in patients with hepatitis C virus (HCV)-HBV dual infection with active hepatitis C who received pegylated interferon-α and ribavirin dual therapy. We enrolled 121 patients with HCV-HBV dual infection after dual therapy. Stored serum was collected before treatment. RT-PCR was used to analyze miR-122. HBsAg seroclearance was noted in 37 (30.1%) cases during a median follow-up period of 5.4 years. miR-122 was significantly lower in HBsAg seroclearance patients than in non-HBsAg seroclearance patients (P < 0.014). Multivariate analysis showed that miR-122 was an independent factor of HBsAg seroclearance (OR: 0.30, 95% CI: 0.09–0.98, P = 0.046). miR-122 was significantly higher in patients who were qHBsAg > 100 IU/mL versus ≤100 IU/mL (P < 0.001). We concluded that in patients with HBV-HCV dual infection with active hepatitis C, miR-122 was associated with HBsAg seroclearance after therapy and qHBsAg level before therapy, indicating that miR-122 plays key roles in modulating HBV replication.
Functional properties of modern engineering products result from merging the geometry and material properties of underlying components into sophisticated overall assemblies. The foundation of this design process is an integration of computer aided design (CAD) tools that allow rapid geometric modifications with robust simulation tools to guide design iterations (i.e. computer-aided engineering, CAE). Recently, DNA has been used to make nanodevices for a myriad of applications across fields including medicine, nanomanufacturing, synthetic biology, biosensing, and biophysics. However, currently these self-assembled DNA nanodevices rely primarily on geometric design, and hence, they have not demonstrated the same sophistication as real-life products. We present an iterative design pipeline for DNA assemblies that integrates CAE based on coarse-grained molecular dynamics with a versatile CAD approach that combines topdown automation with bottom-up control over geometry. This intuitive framework redefines the scope of structural complexity and enhances mechanical and dynamic design of DNA assemblies. Main Text:Combining computer aided design (CAD) with computer aided engineering (CAE) 1 (i.e. iterative design guided by simulation) into Integrated Computational Materials Engineering (ICME) frameworks 2,3 is essential to integrate consideration of material properties and geometric design across multiple length scales. ICME has been well studied for tailoring performance metrics 2 of traditional engineering materials such as alloys and composites 4 . In contrast, integrating CAD and CAE for biomolecular self-assembly has remained elusive. Computationally-guided design of proteins is well-established 5 , but the diversity of structures and complexity of the interactions that govern self-assembly impede the development of geometric CAD. On the other hand, CAD tools that capture the structure and interactions of DNA have been essential to facilitating structural DNA nanotechnology 6-9 , but currently these approaches rely purely on geometric design. The recent emergence of high fidelity coarse-grained molecular dynamics (MD) simulation tools for DNA nanostructures 10-15 provide an opportunity to realize CAE for DNA-based design to enable systems with new levels of structural complexity that can also be tailored for functional properties such as reconfiguration, mechanical properties, or stimulus response. Here we present an ICME approach for DNA assemblies that relies on a custom CAD tool with several features that enhance the scope of geometric design and facilitate tight integration with coarse-grained MD models [10][11][12] to enable CAE for complex DNA assemblies.The precise control over geometry of DNA assemblies 16-19 make them highly attractive for applications such as drug delivery 20 , templating a variety of materials or molecules 21-25 , nanoscale measurement tools 26,27 , and molecular robotics 28-33 . However, DNA-based design approaches have largely overlooked material properties, which limits the structural, ...
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