scholarly journals Nucleic acid-based nanoengineering: novel structures for biomedical applications

2011 ◽  
Vol 1 (5) ◽  
pp. 702-724 ◽  
Author(s):  
Hanying Li ◽  
Thomas H. LaBean ◽  
Kam W. Leong

Nanoengineering exploits the interactions of materials at the nanometre scale to create functional nanostructures. It relies on the precise organization of nanomaterials to achieve unique functionality. There are no interactions more elegant than those governing nucleic acids via Watson–Crick base-pairing rules. The infinite combinations of DNA/RNA base pairs and their remarkable molecular recognition capability can give rise to interesting nanostructures that are only limited by our imagination. Over the past years, creative assembly of nucleic acids has fashioned a plethora of two-dimensional and three-dimensional nanostructures with precisely controlled size, shape and spatial functionalization. These nanostructures have been precisely patterned with molecules, proteins and gold nanoparticles for the observation of chemical reactions at the single molecule level, activation of enzymatic cascade and novel modality of photonic detection, respectively. Recently, they have also been engineered to encapsulate and release bioactive agents in a stimulus-responsive manner for therapeutic applications. The future of nucleic acid-based nanoengineering is bright and exciting. In this review, we will discuss the strategies to control the assembly of nucleic acids and highlight the recent efforts to build functional nucleic acid nanodevices for nanomedicine.

2020 ◽  
Vol 9 (1) ◽  
pp. 1118-1136
Author(s):  
Zhenjia Huang ◽  
Gary Chi-Pong Tsui ◽  
Yu Deng ◽  
Chak-Yin Tang

AbstractMicro/nano-fabrication technology via two-photon polymerization (TPP) nanolithography is a powerful and useful manufacturing tool that is capable of generating two dimensional (2D) to three dimensional (3D) arbitrary micro/nano-structures of various materials with a high spatial resolution. This technology has received tremendous interest in cell and tissue engineering and medical microdevices because of its remarkable fabrication capability for sophisticated structures from macro- to nano-scale, which are difficult to be achieved by traditional methods with limited microarchitecture controllability. To fabricate precisely designed 3D micro/nano-structures for biomedical applications via TPP nanolithography, the use of photoinitiators (PIs) and photoresists needs to be considered comprehensively and systematically. In this review, widely used commercially available PIs are first discussed, followed by elucidating synthesis strategies of water-soluble initiators for biomedical applications. In addition to the conventional photoresists, the distinctive properties of customized stimulus-responsive photoresists are discussed. Finally, current limitations and challenges in the material and fabrication aspects and an outlook for future prospects of TPP for biomedical applications based on different biocompatible photosensitive composites are discussed comprehensively. In all, this review provides a basic understanding of TPP technology and important roles of PIs and photoresists for fabricating high-precision stimulus-responsive micro/nano-structures for a wide range of biomedical applications.


2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Yukiko Kamiya ◽  
Tadashi Satoh ◽  
Atsuji Kodama ◽  
Tatsuya Suzuki ◽  
Keiji Murayama ◽  
...  

Abstract Xeno nucleic acids, which are synthetic analogues of natural nucleic acids, have potential for use in nucleic acid drugs and as orthogonal genetic biopolymers and prebiotic precursors. Although few acyclic nucleic acids can stably bind to RNA and DNA, serinol nucleic acid (SNA) and L-threoninol nucleic acid (L-aTNA) stably bind to them. Here we disclose crystal structures of RNA hybridizing with SNA and with L-aTNA. The heteroduplexes show unwound right-handed helical structures. Unlike canonical A-type duplexes, the base pairs in the heteroduplexes align perpendicularly to the helical axes, and consequently helical pitches are large. The unwound helical structures originate from interactions between nucleobases and neighbouring backbones of L-aTNA and SNA through CH–O bonds. In addition, SNA and L-aTNA form a triplex structure via C:G*G parallel Hoogsteen interactions with RNA. The unique structural features of the RNA-recognizing mode of L-aTNA and SNA should prove useful in nanotechnology, biotechnology, and basic research into prebiotic chemistry.


Nanoscale ◽  
2015 ◽  
Vol 7 (14) ◽  
pp. 5998-6006 ◽  
Author(s):  
M. Aramesh ◽  
O. Shimoni ◽  
K. Fox ◽  
T. J. Karle ◽  
A. Lohrmann ◽  
...  

Single-molecule-detection, selectivity, broad-range detection and biocompatibility are achieved using nanoporous diamond-like carbon coated oxide membranes.


Todd has made highly significant contributions to the chemistry of natural products, in particular in relation to compounds which play important roles in biological systems. His researches on vitamins B 1 , E and B 12 were most elegant and have had far-reaching implications, but none more so than his structural and synthetic studies in the nucleic acid field. Here he developed methods for the synthesis of the nucleosides and for their phosphorylation; his work on the way they are combined made possible the subsequent determination of the three-dimensional structure of the nucleic acids thereby providing the basis for much of the exciting activity in the nucleotide field today. Todd’s achievements arise out of a rare combination of theoretical knowledge and outstanding experimental skill, with the most judicious exploitation of modern techniques. His work and his quality as an investigator have been widely recognized by biologists as well as by organic chemists.


2008 ◽  
Vol 82 (20) ◽  
pp. 10129-10142 ◽  
Author(s):  
Kristen M. Stewart-Maynard ◽  
Margareta Cruceanu ◽  
Fei Wang ◽  
My-Nuong Vo ◽  
Robert J. Gorelick ◽  
...  

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) nucleocapsid protein (NC) is a nucleic acid chaperone that facilitates the remodeling of nucleic acids during various steps of the viral life cycle. Two main features of NC's chaperone activity are its abilities to aggregate and to destabilize nucleic acids. These functions are associated with NC's highly basic character and with its zinc finger domains, respectively. While the chaperone activity of HIV-1 NC has been extensively studied, less is known about the chaperone activities of other retroviral NCs. In this work, complementary experimental approaches were used to characterize and compare the chaperone activities of NC proteins from four different retroviruses: HIV-1, Moloney murine leukemia virus (MLV), Rous sarcoma virus (RSV), and human T-cell lymphotropic virus type 1 (HTLV-1). The different NCs exhibited significant differences in their overall chaperone activities, as demonstrated by gel shift annealing assays, decreasing in the order HIV-1 ∼ RSV > MLV ≫ HTLV-1. In addition, whereas HIV-1, RSV, and MLV NCs are effective aggregating agents, HTLV-1 NC, which exhibits poor overall chaperone activity, is unable to aggregate nucleic acids. Measurements of equilibrium binding to single- and double-stranded oligonucleotides suggested that all four NC proteins have moderate duplex destabilization capabilities. Single-molecule DNA-stretching studies revealed striking differences in the kinetics of nucleic acid dissociation between the NC proteins, showing excellent correlation between nucleic acid dissociation kinetics and overall chaperone activity.


2021 ◽  
Author(s):  
Filip N Boskovic ◽  
Ulrich Felix Keyser

Identifying RNA transcript isoforms requires intricate protocols that suffer from various enzymatic biases. Here we design three-dimensional molecular constructs that enable identification of transcript isoforms at the single-molecule level using solid-state nanopore microscopy. We refold target RNA into RNA identifiers (IDs) with designed sets of complementary DNA strands. Each reshaped molecule carries a unique sequence of structural (pseudo)colors. Structural colors consist of DNA structures, protein labels, native RNA structures, or a combination of all three. The sequence of structural colors of RNA IDs enables simultaneous identification and relative quantification of multiple RNA targets without prior amplification. Our Amplification-free RNA TargEt Multiplex Isoform Sensing (ARTEMIS) reveals structural arrangements in native transcripts in agreement with published variants. ARTEMIS discriminates circular and linear transcript isoforms in a one step, enzyme-free reaction in a complex human transcriptome using single-molecule readout.


2021 ◽  
Author(s):  
Keisuke Shimizu ◽  
Batsaikhan Mijiddorj ◽  
Masataka Usami ◽  
Shuhei Yoshida ◽  
Shiori Akayama ◽  
...  

Abstract The amino acid sequence of a protein encodes information on its three-dimensional structure and specific functionality. De novo protein design has emerged as a method to manipulate the primary structure for the development of artificial proteins and peptides with desired functionality. This paper describes the de novo design of a pore-forming peptide that has a β-hairpin structure and assembles to form a stable nanopore in a bilayer lipid membrane. This large synthetic nanopore is an entirely artificial device with practical applications. This peptide, named SV28, forms nanopore structures ranging from 1.6 to 6.2 nm in diameter assembled from 7 to 18 monomers. The nanopore formed with a diameter of 5 nm is able to detect long double-stranded DNA (dsDNA) with 1 kbp length. Moreover, the larger sized nanopore can discriminate and human telomeric DNA (G-quadruplex, G4). The blocking current signals allowed us to investigate the translocation behavior of dsDNA or G4 structure at the single molecule level. Such de novo design of peptide sequences has the potential to create novel nanopores, which would be applicable in molecular transporter between across lipid membrane.


The Copley Medal is awarded to Lord Todd, F. R. S. Todd has made highly significant contributions to the chemistry of natural products, in particular in relation to compounds which play important roles in biological systems. His researches on vitamins B 1 , E and B 12 were most elegant and have had far-reaching implications, but none more so than his structural and synthetic studies in the nucleic acid field. Here he developed methods for the synthesis of the nucleosides and for their phosphorylation; his work on the way they are combined made possible the subsequent determination of the three-dimensional structure of the nucleic acids thereby providing the basis for much of the exciting activity in the nucleotide field today. Todd’s achievements arise out of a rare combination of theoretical knowledge and outstanding experimental skill, with the most judicious exploitation of modern techniques. His work and his quality as an investigator have been widely recognized by biologists as well as by organic chemists.


2020 ◽  
Author(s):  
Keisuke Shimizu ◽  
Batsaikhan Mijiddorj ◽  
Shuhei Yoshida ◽  
Shiori Akayama ◽  
Yoshio Hamada ◽  
...  

The amino acid sequence of a protein encodes information on its three-dimensional structure and specific functionality. De novo protein design has emerged as a method to manipulate the primary structure for the development of artificial proteins and peptides with desired functionality. This paper describes the de novo design of a pore-forming peptide that has a β-hairpin structure and assembles to form a stable nanopore in a bilayer lipid membrane. This large synthetic nanopore is an entirely artificial device with practical applications. This peptide, named SV28, forms nanopore structures ranging from 1.6 to 6.2 nm in diameter assembled from 7 to 18 monomers. The nanopore formed with a diameter of 5 nm is able to detect long double-stranded DNA (dsDNA) with 1 kbp length, and measurement of current signals allowed us to investigate the translocation behavior of dsDNA at the single molecule level. Such de novo design of peptide sequences has the potential to create assembled structure in lipid membrane such as novel nanopores, which would also be applicable in molecular transporter between inside and outside of lipid membrane.


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