Department of Computer Science, Duke University, Durham, NC, USA.
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.
Sci Adv. 2022 Dec 23;8(51):eade4455. doi: 10.1126/sciadv.ade4455.
Improving the precision and function of encapsulating three-dimensional (3D) DNA nanostructures via curved geometries could have transformative impacts on areas such as molecular transport, drug delivery, and nanofabrication. However, the addition of non-rasterized curvature escalates design complexity without algorithmic regularity, and these challenges have limited the ad hoc development and usage of previously unknown shapes. In this work, we develop and automate the application of a set of previously unknown design principles that now includes a multilayer design for closed and curved DNA nanostructures to resolve past obstacles in shape selection, yield, mechanical rigidity, and accessibility. We design, analyze, and experimentally demonstrate a set of diverse 3D curved nanoarchitectures, showing planar asymmetry and examining partial multilayer designs. Our automated design tool implements a combined algorithmic and numerical approximation strategy for scaffold routing and crossover placement, which may enable wider applications of general DNA nanostructure design for nonregular or oblique shapes.
通过弯曲几何形状来提高封装三维（3D）DNA 纳米结构的精度和功能，可以在分子运输、药物输送和纳米制造等领域产生变革性的影响。然而，非光栅化曲率的增加会增加设计的复杂性，而没有算法规则，这些挑战限制了以前未知形状的临时开发和使用。在这项工作中，我们开发并自动化应用了一组以前未知的设计原则，现在包括用于封闭和弯曲 DNA 纳米结构的多层设计，以解决过去在形状选择、产量、机械刚性和可及性方面的障碍。我们设计、分析和实验证明了一系列不同的 3D 弯曲纳米结构，展示了平面不对称性并检查了部分多层设计。我们的自动化设计工具实现了支架布线和交叉放置的组合算法和数值逼近策略，这可能为非规则或倾斜形状的通用 DNA 纳米结构设计提供更广泛的应用。
