Oliver Ryan C, Rolband Lewis A, Hutchinson-Lundy Alanna M, Afonin Kirill A, Krueger Joanna K
Neutron Scattering Division, Oak Ridge National Laboratory, Oak Ridge, TN 37830, USA.
UNC Charlotte Chemistry Department, Charlotte, NC 28223, USA.
Nanomaterials (Basel). 2019 May 2;9(5):681. doi: 10.3390/nano9050681.
Nucleic acid-based technologies are an emerging research focus area for pharmacological and biological studies because they are biocompatible and can be designed to produce a variety of scaffolds at the nanometer scale. The use of nucleic acids (ribonucleic acid (RNA) and/or deoxyribonucleic acid (DNA)) as building materials in programming the assemblies and their further functionalization has recently established a new exciting field of RNA and DNA nanotechnology, which have both already produced a variety of different functional nanostructures and nanodevices. It is evident that the resultant architectures require detailed structural and functional characterization and that a variety of technical approaches must be employed to promote the development of the emerging fields. Small-angle X-ray and neutron scattering (SAS) are structural characterization techniques that are well placed to determine the conformation of nucleic acid nanoparticles (NANPs) under varying solution conditions, thus allowing for the optimization of their design. SAS experiments provide information on the overall shapes and particle dimensions of macromolecules and are ideal for following conformational changes of the molecular ensemble as it behaves in solution. In addition, the inherent differences in the neutron scattering of nucleic acids, lipids, and proteins, as well as the different neutron scattering properties of the isotopes of hydrogen, combined with the ability to uniformly label biological macromolecules with deuterium, allow one to characterize the conformations and relative dispositions of the individual components within an assembly of biomolecules. This article will review the application of SAS methods and provide a summary of their successful utilization in the emerging field of NANP technology to date, as well as share our vision on its use in complementing a broad suite of structural characterization tools with some simulated results that have never been shared before.
基于核酸的技术是药理学和生物学研究中一个新兴的研究重点领域，因为它们具有生物相容性，并且可以设计成在纳米尺度上产生各种支架。在对组装体进行编程及其进一步功能化过程中使用核酸（核糖核酸（RNA）和/或脱氧核糖核酸（DNA））作为构建材料，最近开创了一个令人兴奋的RNA和DNA纳米技术新领域，这两个领域都已经产生了各种不同的功能纳米结构和纳米器件。显然，所得的结构需要详细的结构和功能表征，并且必须采用多种技术方法来促进这些新兴领域的发展。小角X射线和中子散射（SAS）是结构表征技术，非常适合在不同溶液条件下确定核酸纳米颗粒（NANP）的构象，从而实现其设计的优化。SAS实验提供了关于大分子整体形状和颗粒尺寸的信息，非常适合跟踪分子聚集体在溶液中的构象变化。此外，核酸、脂质和蛋白质在中子散射方面的固有差异，以及氢同位素不同的中子散射特性，再加上用氘均匀标记生物大分子的能力，使得人们能够表征生物分子组装体内各个组分的构象和相对位置。本文将回顾SAS方法的应用，并总结其迄今为止在NANP技术新兴领域中的成功应用，同时分享我们对其在补充一系列广泛的结构表征工具方面的应用展望，并给出一些从未公开过的模拟结果。
