Biological applications of xeno nucleic acids

2017 ◽  
Vol 13 (2) ◽  
pp. 235-245 ◽  
Author(s):  
Kunihiko Morihiro ◽  
Yuuya Kasahara ◽  
Satoshi Obika
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Antisense Oligonucleotides ◽  
Biological Applications ◽  
Chemically Modified ◽  
Nucleic Acid Analogues

Xeno nucleic acids (XNAs) are a group of chemically modified nucleic acid analogues that have been applied to various biological technologies such as antisense oligonucleotides, siRNAs and aptamers.

Investigation of twisted intercalating nucleic acid (TINA)-modified antisense oligonucleotides for splice modulation by induced exon-skipping in vitro

RSC Advances ◽  
2016 ◽  
Vol 6 (97) ◽  
pp. 95169-95172 ◽  
Author(s):  
Bao T. Le ◽  
Vyacheslav V. Filichev ◽  
Rakesh N. Veedu
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Antisense Oligonucleotides ◽  
Exon Skipping

We have investigated the applicability of twisted intercalating nucleic acids (TINA)-modified antisense oligonucleotides (AOs) in exon skipping. We found that TINA-modified AOs induced exon skipping.

Nucleic Acid Therapeutics in Huntington’s Disease

2019 ◽  
Vol 13 (3) ◽  
pp. 187-206 ◽  
Author(s):  
Kuljit Singh ◽  
Ipsita Roy
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Protein Aggregation ◽  
Huntington's Disease ◽  
Antisense Oligonucleotides ◽  
Protein Misfolding ◽  
Mutant Protein ◽  
Mutant Huntingtin ◽  
Nucleic Acid Therapeutics ◽  
Delivery Techniques

Background: Protein misfolding is a critical factor in the progression of a large number of neurodegenerative diseases. The incorrectly folded protein is prone to aggregation, leading to aberrant interaction with other cellular proteins, elevated oxidative stress, impaired cellular machinery, finally resulting in cell death. Due to its monogenic origin, Huntington’s disease (HD) is a poster child of protein misfolding neurodegenerative disorders. The presence of neuronal inclusions of mutant huntingtin N-terminal fragments, mainly in the cortex and striatum, is a neuropathological hallmark of HD. Inhibition of protein misfolding and aggregation has been attempted using a variety of conventional protein stabilizers. Methods: This review describes how, in recent times, nucleic acid therapeutics has emerged as a selective tool to downregulate the aberrant transcript and reduce expression of mutant huntingtin, thereby alleviating protein aggregation. Different strategies of use of nucleic acids, including antisense oligonucleotides, short inhibitory RNA sequences and aptamers have been discussed. The following patent databases were consulted: European Patent Office (EPO), the United States Patent and Trademark Office (USPTO), Patent scope Search International and National Patent Collections (WIPO) and Google Patents. Results: Tools such as RNA interference (RNAi) and antisense oligonucleotides (ASOs) are potential therapeutic agents which target the post-transcriptional step, accelerating mRNA degradation and inhibiting the production of the mutant protein. These nucleic acid sequences not only target the elongated CAG triplet repeat translating to an expanded polyglutamine tract in the mutant protein, but have also been used to target single nucleotide polymorphisms associated with the mutant allele. The therapeutic sequences have been investigated in a number of cells and animal models of HD. One antisense sequence, with desirable safety properties, has recently shown downregulation of huntingtin protein in a limited clinical trial. RNA aptamers have also shown promising results in inhibiting protein aggregation in a yeast model of HD. Novel drug delivery techniques have been employed to overcome the blood brain barrier for the use of these therapeutic sequences. Conclusion: The selectivity and specificity imparted by nucleic acids, along with novel delivery techniques, make them hopeful candidates for the development of a curative strategy for HD.

Advances in the synthesis and antisense technology applications of bridged nucleic acid monomers

2021 ◽  
Vol 25 ◽  
Author(s):  
Priyanka Mangla ◽  
Balaji Olety ◽  
Vivek K. Sharma
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Antisense Oligonucleotides ◽  
Cost Effective ◽  
Biophysical Properties ◽  
Technology Applications ◽  
Effective Synthesis ◽  
Target Rna ◽  
Ribose Sugar ◽  
Tremendous Impact

: Bridged nucleic acids (BNA) or locked nucleic acids (LNA) are a class of nucleic acids modification, which is obtained by connecting the 2'-O and 4'-C of ribose sugar using a methylene bridge. This ‘bridging or locking’ (hence the name) of ribose sugar has a tremendous impact both on the biological and biophysical properties of therapeutic nucleic acids. They have enhanced stability against nucleases and also have higher binding affinity for the target RNA. Owing to these advantages, BNA is one of the most preferred nucleic acid modifications of antisense oligonucleotides (ASOs). However, the synthesis of BNA monomers which are lengthy and low-yielding, requires extensive protection and deprotection of the sugar functionalities. In this article, we aim to review challenges associated with their synthesis, and discuss recent chemical, chemo-enzymatic, and transglycosylation strategies employed for efficient and cost-effective synthesis of BNA monomers and selected BNA analogues.

scholarly journals Artificial Specific Binders Directly Recovered from Chemically Modified Nucleic Acid Libraries

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Yuuya Kasahara ◽  
Masayasu Kuwahara
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Biological Research ◽  
Future Research ◽  
Chemical Modifications ◽  
Additional Time ◽  
Nucleotide Analogs ◽  
Enzymatic Production ◽  
Chemically Modified ◽  
Nucleic Acid Aptamers

Specific binders comprised of nucleic acids, that is, RNA/DNA aptamers, are attractive functional biopolymers owing to their potential broad application in medicine, food hygiene, environmental analysis, and biological research. Despite the large number of reports on selection of natural DNA/RNA aptamers, there are not many examples of direct screening of chemically modified nucleic acid aptamers. This is because of (i) the inferior efficiency and accuracy of polymerase reactions involving transcription/reverse-transcription of modified nucleotides compared with those of natural nucleotides, (ii) technical difficulties and additional time and effort required when using modified nucleic acid libraries, and (iii) ambiguous efficacies of chemical modifications in binding properties until recently; in contrast, the effects of chemical modifications on biostability are well studied using various nucleotide analogs. Although reports on the direct screening of a modified nucleic acid library remain in the minority, chemical modifications would be essential when further functional expansion of nucleic acid aptamers, in particular for medical and biological uses, is considered. This paper focuses on enzymatic production of chemically modified nucleic acids and their application to random screenings. In addition, recent advances and possible future research are also described.

Amido-bridged nucleic acids with small hydrophobic residues enhance hepatic tropism of antisense oligonucleotides in vivo

2015 ◽  
Vol 13 (12) ◽  
pp. 3757-3765 ◽  
Author(s):  
Tsuyoshi Yamamoto ◽  
Aiko Yahara ◽  
Reiko Waki ◽  
Hidenori Yasuhara ◽  
Fumito Wada ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Building Block ◽  
Antisense Oligonucleotides ◽  
Hydrophobic Residues ◽  
Pharmacokinetic Properties ◽  
High Scalability ◽  
Small Hydrophobic

High scalability of a novel bicyclic nucleoside building block, amido-bridged nucleic acid (AmNA), to diversify pharmacokinetic properties of therapeutic antisense oligonucleotides is described.

scholarly journals Advances in Therapeutic L-Nucleosides and L-Nucleic Acids with Unusual Handedness

Genes ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 46
Author(s):  
Yuliya Dantsu ◽  
Ying Zhang ◽  
Wen Zhang
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Tertiary Structures ◽  
Chemically Modified ◽  
Naturally Occurring ◽  
Modified Dna ◽  
Target Binding ◽  
Oligonucleotide Analogues ◽  
Drug Delivery Devices

Nucleic-acid-based small molecule and oligonucleotide therapies are attractive topics due to their potential for effective target of disease-related modules and specific control of disease gene expression. As the non-naturally occurring biomolecules, modified DNA/RNA nucleoside and oligonucleotide analogues composed of L-(deoxy)riboses, have been designed and applied as innovative therapeutics with superior plasma stability, weakened cytotoxicity, and inexistent immunogenicity. Although all the chiral centers in the backbone are mirror converted from the natural D-nucleic acids, L-nucleic acids are equipped with the same nucleobases (A, G, C and U or T), which are critical to maintain the programmability and form adaptable tertiary structures for target binding. The types of L-nucleic acid drugs are increasingly varied, from chemically modified nucleoside analogues that interact with pathogenic polymerases to nanoparticles containing hundreds of repeating L-nucleotides that circulate durably in vivo. This article mainly reviews three different aspects of L-nucleic acid therapies, including pharmacological L-nucleosides, Spiegelmers as specific target-binding aptamers, and L-nanostructures as effective drug-delivery devices.

scholarly journals Rational design of an XNA ligase through docking of unbound nucleic acids to toroidal proteins

2019 ◽  
Vol 47 (13) ◽  
pp. 7130-7142 ◽  
Author(s):  
Michiel Vanmeert ◽  
Jamoliddin Razzokov ◽  
Muhammad Usman Mirza ◽  
Stephen D Weeks ◽  
Guy Schepers ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Rational Design ◽  
Dna Ligase ◽  
Processing Enzymes ◽  
First Approximation ◽  
Acid Processing ◽  
First Time ◽  
Nucleic Acid Analogues

AbstractXenobiotic nucleic acids (XNA) are nucleic acid analogues not present in nature that can be used for the storage of genetic information. In vivo XNA applications could be developed into novel biocontainment strategies, but are currently limited by the challenge of developing XNA processing enzymes such as polymerases, ligases and nucleases. Here, we present a structure-guided modelling-based strategy for the rational design of those enzymes essential for the development of XNA molecular biology. Docking of protein domains to unbound double-stranded nucleic acids is used to generate a first approximation of the extensive interaction of nucleic acid processing enzymes with their substrate. Molecular dynamics is used to optimise that prediction allowing, for the first time, the accurate prediction of how proteins that form toroidal complexes with nucleic acids interact with their substrate. Using the Chlorella virus DNA ligase as a proof of principle, we recapitulate the ligase's substrate specificity and successfully predict how to convert it into an XNA-templated XNA ligase.

Nucleic Acid Molecules Prepared by Monolayer Techniques

1972 ◽  
Vol 30 ◽  
pp. 178-179
Author(s):  
Dimitrij Lang
Keyword(s):  
Electron Microscopy ◽  
Standard Deviation ◽  
Nucleic Acid ◽  
Cytochrome C ◽  
Nucleic Acids ◽  
Contour Length ◽  
Sample Standard Deviation ◽  
Molecular Weights ◽  
Length Measurements ◽  
Protein Monolayer

The success of the protein monolayer technique for electron microscopy of individual DNA molecules is based on the prevention of aggregation and orientation of the molecules during drying on specimen grids. DNA adsorbs first to a surface-denatured, insoluble cytochrome c monolayer which is then transferred to grids, without major distortion, by touching. Fig. 1 shows three basic procedures which, modified or not, permit the study of various important properties of nucleic acids, either in concert with other methods or exclusively:1) Molecular weights relative to DNA standards as well as number distributions of molecular weights can be obtained from contour length measurements with a sample standard deviation between 1 and 4%.

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