scholarly journals Barcoding chemical modifications into nucleic acids improves drug stability in vivo

2018 ◽  
Vol 6 (44) ◽  
pp. 7197-7203 ◽  
Author(s):  
Cory D. Sago ◽  
Sujay Kalathoor ◽  
Jordan P. Fitzgerald ◽  
Gwyneth N. Lando ◽  
Naima Djeddar ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Drug Stability ◽  
Chemical Modifications

The efficacy of nucleic acid therapies can be limited by unwanted degradation.

scholarly journals Modified Nucleic Acids: Expanding the Capabilities of Functional Oligonucleotides

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4659 ◽  
Author(s):  
Steven Ochoa ◽  
Valeria T. Milam
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Chemical Structure ◽  
Chemical Diversity ◽  
Physiochemical Properties ◽  
Phosphate Backbone ◽  
Modified Nucleic Acids ◽  
Recent Developments ◽  
Diagnostic Applications

In the last three decades, oligonucleotides have been extensively investigated as probes, molecular ligands and even catalysts within therapeutic and diagnostic applications. The narrow chemical repertoire of natural nucleic acids, however, imposes restrictions on the functional scope of oligonucleotides. Initial efforts to overcome this deficiency in chemical diversity included conservative modifications to the sugar-phosphate backbone or the pendant base groups and resulted in enhanced in vivo performance. More importantly, later work involving other modifications led to the realization of new functional characteristics beyond initial intended therapeutic and diagnostic prospects. These results have inspired the exploration of increasingly exotic chemistries highly divergent from the canonical nucleic acid chemical structure that possess unnatural physiochemical properties. In this review, the authors highlight recent developments in modified oligonucleotides and the thrust towards designing novel nucleic acid-based ligands and catalysts with specifically engineered functions inaccessible to natural oligonucleotides.

The reaction of the psoralens with deoxyribonucleic acid

1984 ◽  
Vol 17 (1) ◽  
pp. 1-44 ◽  
Author(s):  
John E. Hearst ◽  
Stephen T. Isaacs ◽  
David Kanne ◽  
Henry Rapoport ◽  
Kenneth Straub
Keyword(s):  
Natural Selection ◽  
Nucleic Acid ◽  
Nucleic Acids ◽  
Chemical Modification ◽  
Deoxyribonucleic Acid ◽  
Molecular Level ◽  
Virus Particles ◽  
Cross Links ◽  
High Concentrations

Psoralen photochemistry is specific for nucleic acids and is better understood at the molecular level than are all other methods of chemical modification of nucleic acids. These compounds are used both for in vivo structure analysis and for photochemotherapy since they easily penetrate both cells and virus particles. Apparently, natural selection has selected for membrane and virus penetrability during the evolution of these natural products. Most cells are unaffected by relatively high concentrations of psoralens in the absence of ultraviolet light, and the metabolites of the psoralens have thus far not created a problem. Finally, psoralens form both monoadduct and cross-links in nucleic acid helices, the yield of each being easily controlled by the conditions used during the photochemistry.

Hydroxyproline-Based DNA Mimics: A Review on Synthesis and Properties

2006 ◽  
Vol 71 (7) ◽  
pp. 929-955 ◽  
Author(s):  
Vladimir A. Efimov ◽  
Oksana G. Chakhmakhcheva
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Phosphonic Acid ◽  
Peptide Nucleic Acids ◽  
Biological Properties ◽  
High Potential ◽  
Physicochemical And Biological Properties

With the aim to improve physicochemical and biological properties of natural oligonucleotides, many types of DNA analogues and mimics are designed on the basis of hydroxyproline and its derivatives, and their properties are evaluated. Among them, two types of DNA mimics representing hetero-oligomers constructed from alternating monomers of phosphono peptide nucleic acids and monomers on the base of trans-1-acetyl-4-hydroxy-L-proline (HypNA-pPNAs) and oligomers constructed from monomers containing (2S,4R)-1-acetyl-4-hydroxypyrrolidine-2-phosphonic acid backbone (pHypNAs) are of particular interest. In a set of in vitro and in vivo assays, it was shown that HypNA-pPNAs and pHypNAs demonstrated a high potential for the use in nucleic acid based diagnostics, isolation of nucleic acids and antisense experiments. A review with 53 references.

scholarly journals Exploring miR-9 Involvement in Ciona intestinalis Neural Development Using Peptide Nucleic Acids

2020 ◽  
Vol 21 (6) ◽  
pp. 2001
Author(s):  
Silvia Mercurio ◽  
Silvia Cauteruccio ◽  
Raoul Manenti ◽  
Simona Candiani ◽  
Giorgio Scarì ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Neural Development ◽  
Peptide Nucleic Acids ◽  
Model Organism ◽  
Ciona Intestinalis ◽  
Transcriptional Level ◽  
Regulate Gene Expression

The microRNAs are small RNAs that regulate gene expression at the post-transcriptional level and can be involved in the onset of neurodegenerative diseases and cancer. They are emerging as possible targets for antisense-based therapy, even though the in vivo stability of miRNA analogues is still questioned. We tested the ability of peptide nucleic acids, a novel class of nucleic acid mimics, to downregulate miR-9 in vivo in an invertebrate model organism, the ascidian Ciona intestinalis, by microinjection of antisense molecules in the eggs. It is known that miR-9 is a well-conserved microRNA in bilaterians and we found that it is expressed in epidermal sensory neurons of the tail in the larva of C. intestinalis. Larvae developed from injected eggs showed a reduced differentiation of tail neurons, confirming the possibility to use peptide nucleic acid PNA to downregulate miRNA in a whole organism. By identifying putative targets of miR-9, we discuss the role of this miRNA in the development of the peripheral nervous system of ascidians.

Clinical Trials of Functional Nucleic Acids

2018 ◽  
Vol 7 (2) ◽  
pp. 46-60 ◽  
Author(s):  
Martina Traykovska ◽  
Sjoerd Miedema ◽  
Robert Penchovsky
Keyword(s):  
Clinical Trials ◽  
Nucleic Acid ◽  
Nucleic Acids ◽  
Pharmaceutical Companies ◽  
Nucleic Acid Therapeutics ◽  
Drug Candidates ◽  
Safety Risks ◽  
Functional Nucleic Acids ◽  
Administration Methods

This chapter describes how functional nucleic acids, such as aptamers, antisense oligonucleotides (ASOs), small interfering (si) RNAs, and ribozymes are considered by some researchers as valuable tools to develop therapeutic agents. They have not been particularly fast in reaching the market as medicines, due to endogenous barriers to extracellular trafficking and cellular uptake of nucleic acids and their inherent instability when applied in vivo. However, research carried out by the nucleic acid engineering community and pharmaceutical companies to circumvent these obstacles has led to the approval of a few aptamers and ASOs as drugs. Nucleic acid therapeutics are usually administered locally to diseased tissue. The drug candidates currently in clinical trials commonly use the same administration methods as previously licensed nucleic acid therapeutics. These administration techniques carry their own safety risks and advantages. In this article, the present state is discussed and prospective options for the use ASOs and aptamers as drugs are listed.

scholarly journals THE INCORPORATION OF FORMATE-C14 INTO THE NUCLEIC ACIDS OF RATS WITH REGENERATING LIVER AND NOVIKOFF HEPATOMA

1959 ◽  
Vol 37 (1) ◽  
pp. 1405-1416 ◽  
Author(s):  
J. C. Nixon ◽  
S. H. Zbarsky
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Mitotic Activity ◽  
Intestinal Mucosa ◽  
Regenerating Liver ◽  
Simultaneous Presence ◽  
Novikoff Hepatoma ◽  
Mitotic Frequency ◽  
Host Tissues

A study was made of the incorporation in vivo of formate-C14 into the purines and thymine of regenerating liver and Novikoff hepatoma in the rat, during the period of maximum mitotic activity of these tissues. The effects of these tissues on one another and on certain host tissues were also studied. The maximum mitotic frequency of Novikoff hepatoma was observed on the 4th day of growth following transplantation. This tumor caused a decrease in formate incorporation into the nucleic acid purines and thymine of the host's spleen and intestinal mucosa but had little effect on liver. The results also indicated that the uptake of formate by the RNA adenine of spleen and intestinal mucosa and the DNA thymine of intestinal mucosa was diminished by the presence of regenerating liver. The simultaneous presence of both regenerating liver and Novikoff hepatoma generally lowered the incorporation of formate-C14 into the nucleic acids of the host spleen and intestinal mucosa. It was observed further that the utilization of formate by the nucleic acids of Novikoff hepatoma and regenerating rat liver was decreased in animals containing both of these rapidly dividing tissues.

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.

scholarly journals Enrichment of Zα domains at cytoplasmic stress granules is due to their innate ability to bind nucleic acids

2021 ◽  
Author(s):  
Luisa Gabriel ◽  
Bharath Srinivasan ◽  
Krzysztof Kuś ◽  
João F. Mata ◽  
Maria João Amorim ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Stress Granules ◽  
Helical Conformation ◽  
Nucleic Acid Binding ◽  
Mobility Shift ◽  
Binding Ability ◽  
Amino Terminal ◽  
Mobility Shift Assay

Zα domains recognize the left-handed helical conformation of double stranded nucleic acids. They are found in proteins involved in the nucleic acid sensory pathway of vertebrate innate immune system and host evasion by viral pathogens. Previously, it has been demonstrated that ADAR1 and DAI localize to the cytosolic stress granules mediated by their Zα domains. To investigate the mechanism, we determined the interactions and localization pattern for the amino-terminal region of human DAI harbouring two Zα domains (ZαβDAI) and a nucleic acid-binding deficient mutant. Electrophoretic mobility shift assay demonstrated the ability of ZαβDAI to bind to hyperedited nucleic acids which are enriched in stress granules. Further, using immunofluorescence and immunoprecipitation coupled with mass-spectrometry, we identified several interacting partners of the ZαβDAI-RNA complex in-vivo under conditions of arsenite-induced stress. These interactions are lost upon loss of nucleic acid binding ability or with RNase treatment. Thus, we posit that the mechanism for the translocation of Zα domain-containing proteins to stress granules is mainly mediated by the nucleic acid binding ability of their Zα domains.

Reversible assembly-disassembly of plasmonic spherical nucleic acid enabling temperature-self-controllable and biomarker-activatable photothermal effect

2021 ◽  
Author(s):  
Lixian Huang ◽  
Jinling Zhang ◽  
Lifang Pang ◽  
Shengqiang Hu ◽  
Liangliang Zhang ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Melting Temperature ◽  
Self Assembly ◽  
The Self ◽  
Photothermal Effect ◽  
Spherical Nucleic Acid ◽  
Photothermal Heating ◽  
Spherical Nucleic Acids

Since the photothermal heating of plasmonic spherical nucleic acids (pSNAs) depended on the self-assembly level and melting temperature (Tm), temperature-self-controllable and biomarker-activatable photothermal effect in vivo was thus achieved using...

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.

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