Applications of Synchrotron‐Based Spectroscopic Techniques in Studying Nucleic Acids and Nucleic Acid‐Functionalized Nanomaterials

Wu, Peiwen; Yu, Yang; McGhee, Claire E.; Tan, Li; Lu, Yi

doi:10.1002/adma.201304891

Cited by 20 publications

(10 citation statements)

References 305 publications

(328 reference statements)

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“…Since then, X-ray diffraction has played a vital role in further discoveries of numerous types of nucleic acid structures. An excellent review of the applications of various synchrotron-based spectroscopic techniques, including small-angle X-ray scattering (SAXS), has been recently published by Yi Lu and his research group [42]. High-resolution techniques such as X-ray crystallography have the capability to provide atomistic structural views.…”

Section: Discussionmentioning

confidence: 99%

Small-Angle Scattering as a Structural Probe for Nucleic Acid Nanoparticles (NANPs) in a Dynamic Solution Environment

et al. 2019

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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.

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Section: Discussionmentioning

confidence: 99%

Small-Angle Scattering as a Structural Probe for Nucleic Acid Nanoparticles (NANPs) in a Dynamic Solution Environment

et al. 2019

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“…So far, not so much research has been performed on the structure of lipid phases comprising mRNA. However, the general understanding of the molecular organization of nucleotide-lipid assemblies as obtained from different DNA lipoplex systems may, at least partially, also be applicable for systems comprising mRNA [24][25][26] .…”

Section: Introductionmentioning

confidence: 99%

Incorporation of mRNA in Lamellar Lipid Matrices for Parenteral Administration

et al. 2018

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Insertion of high molecular weight messenger RNA (mRNA) into lyotropic lipid phases as model systems for controlled release formulations for the mRNA was investigated. Low fractions of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) were used as an anchor to load the mRNA into a lamellar lipid matrix. Dispersions of zwitterionic lipid in the aqueous phase in the presence of increasing fractions of mRNA and cationic lipid were prepared, and the molecular organization was investigated as a function of mRNA and cationic lipid fraction. Insertion of both cationic lipid and mRNA was clearly proven from the physicochemical characteristics. The d-spacing of the lipid bilayers, as determined by small-angle X-ray scattering (SAXS) measurements, responded sensitively to the amount of inserted DOTAP and mRNA. A concise model of the insertion of the mRNA in the lipid matrices was derived, indicating that the mRNA was accommodated in the aqueous slab between lipid bilayers. Depending on the DOTAP and mRNA fraction, a different excess of water was present in this slab. Results from further physicochemical characterization, including determination of free and bound mRNA, zeta potential, and calorimetry data, were in line with this assumption. The structure of these concentrated lipid/mRNA preparations was maintained upon dilution. The functionality of the inserted mRNA was proven by cell culture experiments using C2C12 murine myoblast cells with the luciferase-encoding mRNA. The described lipid phases as carriers for the mRNA may be applicable for different routes of local administration, where control of the release kinetics and the form of the released mRNA (bound or free) is required.

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“…Theoretical and quantum-mechanical calculations of spectra have not yet been successfully applied to nucleic acids as well as polysaccharides and proteins due to various complex overlapping electronic excitations, but theoretical calculations of CD are in better agreement with experiments in the VUV region [ 138 ]. VUVCD spectroscopy of nucleic acids has been developed in parallel with comparative analyses of synthetic polynucleotides composed of selected bases [ 21 , 139 – 145 ].…”

Section: Structural Analysis Of Nucleic Acidsmentioning

confidence: 99%

Synchrotron-radiation vacuum-ultraviolet circular dichroism spectroscopy in structural biology: an overview

Gekko

2019

BIOPHYSICS

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Circular dichroism spectroscopy is widely used for analyzing the structures of chiral molecules, including biomolecules. Vacuum-ultraviolet circular dichroism (VUVCD) spectroscopy using synchrotron radiation can extend the short-wavelength limit into the vacuum-ultraviolet region (down to ~160 nm) to provide detailed and new information about the structures of biomolecules in combination with theoretical analysis and bioinformatics. The VUVCD spectra of saccharides can detect the high-energy transitions of chromophores such as hydroxy and acetal groups, disclosing the contributions of inter- or intramolecular hydrogen bonds to the equilibrium configuration of monosaccharides in aqueous solution. The roles of hydration in the fluctuation of the dihedral angles of carboxyl and amino groups of amino acids can be clarified by comparing the observed VUVCD spectra with those calculated theoretically. The VUVCD spectra of proteins markedly improves the accuracy of predicting the contents and number of segments of the secondary structures, and their amino acid sequences when combined with bioinformatics, for not only native but also nonnative and membrane-bound proteins. The VUVCD spectra of nucleic acids confirm the contributions of the base composition and sequence to the conformation in comparative analyses of synthetic poly-nucleotides composed of selected bases. This review surveys these recent applications of synchrotron-radiation VUVCD spectroscopy in structural biology, covering saccharides, amino acids, proteins, and nucleic acids.

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Applications of Synchrotron‐Based Spectroscopic Techniques in Studying Nucleic Acids and Nucleic Acid‐Functionalized Nanomaterials

Cited by 20 publications

References 305 publications

Small-Angle Scattering as a Structural Probe for Nucleic Acid Nanoparticles (NANPs) in a Dynamic Solution Environment

Small-Angle Scattering as a Structural Probe for Nucleic Acid Nanoparticles (NANPs) in a Dynamic Solution Environment

Incorporation of mRNA in Lamellar Lipid Matrices for Parenteral Administration

Synchrotron-radiation vacuum-ultraviolet circular dichroism spectroscopy in structural biology: an overview

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