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Future Challenges and Trends of Nucleic Acids
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Future Challenges and Trends of Nucleic Acids

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (15 September 2023) | Viewed by 13263

Special Issue Editors

Dr. Annalisa Masi

E-Mail Website
Guest Editor
Institute of Crystallography, Consiglio Nazionale delle Ricerche, Monterotondo Stazione, 00015 Rome, Italy
Interests: design and synthesis of oligonucleotides; oxidative DNA damage and repair; diagnostic; biomarkers with special interest towards cyclopurines and 8-oxo-dG
Special Issues, Collections and Topics in MDPI journals
Dr. Barbara Pascucci

E-Mail Website
Guest Editor
Institute of Crystallography, Consiglio Nazionale delle Ricerche, Monterotondo Stazione, 00015 Rome, Italy
Interests: DNA repair; mitochondrial dysfunction; oxidative stress; aging; neurodegenerative diseases
Special Issues, Collections and Topics in MDPI journals
Dr. Maria Moccia

E-Mail Website
Guest Editor
Institute of Crystallography, Consiglio Nazionale delle Ricerche, Bari, Via G. Ammendola 122/O, 70126 Bari, Italy
Interests: design, synthesis, and development of PNA; miRNAs; therapeutics; diagnostic; cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Oligonucleotides (ODNs) are versatile biopolymers that have emerged as powerful materials for use in basic research and clinical applications. The synthetic accessibility and wide functionality of nucleic acids make them attractive tools for use in a vast array of applications ranging from the technological field (new materials, catalysis, and data storage) to the medical one. In this context, nucleic acid research is taking new directions such as: i) the synthesis and applications of chemically modified oligonucleotides including peptide nucleic acid (PNA), morpholino and locked nucleic acid (LNA), as well as glycol nucleic acid (GNA) and xeno nucleic acid (XNA); ii) nucleic-acid-based therapeutics (aptamers, CRISPR/Cas9, and the use of modified mRNA for protein overexpression); iii) the study of DNA damage and repair; iv) the development of highly sophisticated analytical methods, in particular liquid chromatography–tandem mass spectrometry (LC-MS/MS) for the detection of DNA lesions in nuclear and mitochondrial DNA; v) the synthesis of new antiviral drugs analogous to nucleosides; vi) the study of the interaction of ODN models (G-quadruplex, TFOs, etc.) with pharmacologically active molecules, proteins, and metal ions.

For this Special Issue, entitled "Future Challenges and Trends of Nucleic Acids", we encourage authors to submit research papers and comprehensive reviews that describe the numerous applications of nucleic acids in areas encompassing diagnostics, therapeutics, and synthetic biology, exploring the directions in which the chemistry and biology of nucleic acids is developing, or is likely to develop, in the near or distant future.

Dr. Annalisa Masi
Dr. Barbara Pascucci
Dr. Maria Moccia 
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • nucleic acid
  • diagnostic markers
  • therapeutic agents
  • DNA damage and repair
  • molecular biology

Published Papers (7 papers)

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Research

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17 pages, 5166 KiB  
Article
Exploring the Binding of Natural Compounds to Cancer-Related G-Quadruplex Structures: From 9,10-Dihydrophenanthrenes to Their Dimeric and Glucoside Derivatives
by Chiara Platella, Andrea Criscuolo, Claudia Riccardi, Rosa Gaglione, Angela Arciello, Domenica Musumeci, Marina DellaGreca and Daniela Montesarchio
Int. J. Mol. Sci. 2023, 24(9), 7765; https://doi.org/10.3390/ijms24097765 - 24 Apr 2023
Cited by 1 | Viewed by 1245
Abstract
In-depth studies on the interaction of natural compounds with cancer-related G-quadruplex structures have been undertaken only recently, despite their high potential as anticancer agents, especially due to their well-known and various bioactivities. In this frame, aiming at expanding the repertoire of natural compounds [...] Read more.
In-depth studies on the interaction of natural compounds with cancer-related G-quadruplex structures have been undertaken only recently, despite their high potential as anticancer agents, especially due to their well-known and various bioactivities. In this frame, aiming at expanding the repertoire of natural compounds able to selectively recognize G-quadruplexes, and particularly focusing on phenanthrenoids, a mini-library including dimeric (1–3) and glucoside (4–5) analogues of 9,10-dihydrophenanthrenes, a related tetrahydropyrene glucoside (6) along with 9,10-dihydrophenanthrene 7 were investigated here by several biophysical techniques and molecular docking. Compounds 3 and 6 emerged as the most selective G-quadruplex ligands within the investigated series. These compounds proved to mainly target the grooves/flanking residues of the hybrid telomeric and parallel oncogenic G-quadruplex models exploiting hydrophobic, hydrogen bond and π-π interactions, without perturbing the main folds of the G-quadruplex structures. Notably, a binding preference was found for both ligands towards the hybrid telomeric G-quadruplex. Moreover, compounds 3 and 6 proved to be active on different human cancer cells in the low micromolar range. Overall, these compounds emerged as useful ligands able to target G-quadruplex structures, which are of interest as promising starting scaffolds for the design of analogues endowed with high and selective anticancer activity. Full article
(This article belongs to the Special Issue Future Challenges and Trends of Nucleic Acids)
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14 pages, 3355 KiB  
Article
FapydG in the Shadow of OXOdG—A Theoretical Study of Clustered DNA Lesions
by Bolesław T. Karwowski
Int. J. Mol. Sci. 2023, 24(6), 5361; https://doi.org/10.3390/ijms24065361 - 10 Mar 2023
Cited by 3 | Viewed by 1146
Abstract
Genetic information, irrespective of cell type (normal or cancerous), is exposed to a range of harmful factors, which can lead to more than 80 different types of DNA damage. Of these, oxoG and FapyG have been identified as the most abundant [...] Read more.
Genetic information, irrespective of cell type (normal or cancerous), is exposed to a range of harmful factors, which can lead to more than 80 different types of DNA damage. Of these, oxoG and FapyG have been identified as the most abundant in normoxic and hypoxic conditions, respectively. This article considers d[AFapyGAOXOGA]*[TCTCT] (oligo-FapyG) with clustered DNA lesions (CDLs) containing both the above types of damage at the M06-2x/6-31++G** level of theory in the condensed phase. Furthermore, the electronic properties of oligo-FapyG were analysed in both equilibrated and non-equilibrated solvation–solute interaction modes. The vertical/adiabatic ionization potential (VIP, AIP) and electron affinity (VEA, AEA) of the investigated ds-oligo were found as follows in [eV]: 5.87/5.39 and −1.41/−2.09, respectively. The optimization of the four ds-DNA spatial geometries revealed that the transFapydG was energetically privileged. Additionally, CDLs were found to have little influence on the ds-oligo structure. Furthermore, for the FapyGC base-pair isolated from the discussed ds-oligo, the ionization potential and electron affinity values were higher than those assigned to OXOGC. Finally, a comparison of the influence of FapyGC and OXOGC on charge transfer revealed that, in contrast to the OXOGC base-pair, which, as expected, acted as a radical cation/anion sink in the oligo-FapyG structure, FapyGC did not significantly affect charge transfer (electron–hole and excess–electron). The results presented below indicate that 7,8-dihydro-8-oxo-2′-deoxyguanosine plays a significant role in charge transfer through ds-DNA containing CDL and indirectly has an influence on the DNA lesion recognition and repair process. In contrast, the electronic properties obtained for 2,6-diamino-4-hydroxy-5-foramido-2′deoxypyrimidine were found to be too weak to compete with OXOG to influence charge transfer through the discussed ds-DNA containing CDL. Because increases in multi-damage site formation are observed during radio- or chemotherapy, understanding their role in the above processes can be crucial for the efficiency and safety of medical cancer treatment. Full article
(This article belongs to the Special Issue Future Challenges and Trends of Nucleic Acids)
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18 pages, 1463 KiB  
Article
Duplex DNA Retains the Conformational Features of Single Strands: Perspectives from MD Simulations and Quantum Chemical Computations
by Amedeo Capobianco, Alessandro Landi and Andrea Peluso
Int. J. Mol. Sci. 2022, 23(22), 14452; https://doi.org/10.3390/ijms232214452 - 21 Nov 2022
Cited by 2 | Viewed by 1390
Abstract
Molecular dynamics simulations and geometry optimizations carried out at the quantum level as well as by quantum mechanical/molecular mechanics methods predict that short, single-stranded DNA oligonucleotides adopt conformations very similar to those observed in crystallographic double-stranded B-DNA, with rise coordinates close to ≈3.3 [...] Read more.
Molecular dynamics simulations and geometry optimizations carried out at the quantum level as well as by quantum mechanical/molecular mechanics methods predict that short, single-stranded DNA oligonucleotides adopt conformations very similar to those observed in crystallographic double-stranded B-DNA, with rise coordinates close to ≈3.3 Å. In agreement with the experimental evidence, the computational results show that DNA single strands rich in adjacent purine nucleobases assume more regular arrangements than poly-thymine. The preliminary results suggest that single-stranded poly-cytosine DNA should also retain a substantial helical order in solution. A comparison of the structures of single and double helices confirms that the B-DNA motif is a favorable arrangement also for single strands. Indeed, the optimal geometry of the complementary single helices is changed to a very small extent in the formation of the duplex. Full article
(This article belongs to the Special Issue Future Challenges and Trends of Nucleic Acids)
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Review

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20 pages, 1234 KiB  
Review
Advances in Nucleic Acid Research: Exploring the Potential of Oligonucleotides for Therapeutic Applications and Biological Studies
by Maria Moccia, Barbara Pascucci, Michele Saviano, Maria Teresa Cerasa, Michael A. Terzidis, Chryssostomos Chatgilialoglu and Annalisa Masi
Int. J. Mol. Sci. 2024, 25(1), 146; https://doi.org/10.3390/ijms25010146 - 21 Dec 2023
Viewed by 2421
Abstract
In recent years, nucleic acids have emerged as powerful biomaterials, revolutionizing the field of biomedicine. This review explores the multifaceted applications of nucleic acids, focusing on their pivotal role in various biomedical applications. Nucleic acids, including deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), [...] Read more.
In recent years, nucleic acids have emerged as powerful biomaterials, revolutionizing the field of biomedicine. This review explores the multifaceted applications of nucleic acids, focusing on their pivotal role in various biomedical applications. Nucleic acids, including deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), possess unique properties such as molecular recognition ability, programmability, and ease of synthesis, making them versatile tools in biosensing and for gene regulation, drug delivery, and targeted therapy. Their compatibility with chemical modifications enhances their binding affinity and resistance to degradation, elevating their effectiveness in targeted applications. Additionally, nucleic acids have found utility as self-assembling building blocks, leading to the creation of nanostructures whose high order underpins their enhanced biological stability and affects the cellular uptake efficiency. Furthermore, this review delves into the significant role of oligonucleotides (ODNs) as indispensable tools for biological studies and biomarker discovery. ODNs, short sequences of nucleic acids, have been instrumental in unraveling complex biological mechanisms. They serve as probes for studying gene expression, protein interactions, and cellular pathways, providing invaluable insights into fundamental biological processes. By examining the synergistic interplay between nucleic acids as powerful biomaterials and ODNs as indispensable tools for biological studies and biomarkers, this review highlights the transformative impact of these molecules on biomedical research. Their versatile applications not only deepen our understanding of biological systems but also are the driving force for innovation in diagnostics and therapeutics, ultimately advancing the field of biomedicine. Full article
(This article belongs to the Special Issue Future Challenges and Trends of Nucleic Acids)
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20 pages, 2513 KiB  
Review
Identification and Interpretation of A-to-I RNA Editing Events in Insect Transcriptomes
by Ye Xu, Jiyao Liu, Tianyou Zhao, Fan Song, Li Tian, Wanzhi Cai, Hu Li and Yuange Duan
Int. J. Mol. Sci. 2023, 24(24), 17126; https://doi.org/10.3390/ijms242417126 - 5 Dec 2023
Cited by 3 | Viewed by 1074
Abstract
Adenosine-to-inosine (A-to-I) RNA editing is the most prevalent RNA modification in the nervous systems of metazoans. To study the biological significance of RNA editing, we first have to accurately identify these editing events from the transcriptome. The genome-wide identification of RNA editing sites [...] Read more.
Adenosine-to-inosine (A-to-I) RNA editing is the most prevalent RNA modification in the nervous systems of metazoans. To study the biological significance of RNA editing, we first have to accurately identify these editing events from the transcriptome. The genome-wide identification of RNA editing sites remains a challenging task. In this review, we will first introduce the occurrence, regulation, and importance of A-to-I RNA editing and then describe the established bioinformatic procedures and difficulties in the accurate identification of these sit esespecially in small sized non-model insects. In brief, (1) to obtain an accurate profile of RNA editing sites, a transcriptome coupled with the DNA resequencing of a matched sample is favorable; (2) the single-cell sequencing technique is ready to be applied to RNA editing studies, but there are a few limitations to overcome; (3) during mapping and variant calling steps, various issues, like mapping and base quality, soft-clipping, and the positions of mismatches on reads, should be carefully considered; (4) Sanger sequencing of both RNA and the matched DNA is the best verification of RNA editing sites, but other auxiliary evidence, like the nonsynonymous-to-synonymous ratio or the linkage information, is also helpful for judging the reliability of editing sites. We have systematically reviewed the understanding of the biological significance of RNA editing and summarized the methodology for identifying such editing events. We also raised several promising aspects and challenges in this field. With insightful perspectives on both scientific and technical issues, our review will benefit the researchers in the broader RNA editing community. Full article
(This article belongs to the Special Issue Future Challenges and Trends of Nucleic Acids)
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24 pages, 1509 KiB  
Review
Development of Engineered-U1 snRNA Therapies: Current Status
by Mariana Gonçalves, Juliana Inês Santos, Maria Francisca Coutinho, Liliana Matos and Sandra Alves
Int. J. Mol. Sci. 2023, 24(19), 14617; https://doi.org/10.3390/ijms241914617 - 27 Sep 2023
Viewed by 1714
Abstract
Splicing of pre-mRNA is a crucial regulatory stage in the pathway of gene expression. The majority of human genes that encode proteins undergo alternative pre-mRNA splicing and mutations that affect splicing are more prevalent than previously thought. Targeting aberrant RNA(s) may thus provide [...] Read more.
Splicing of pre-mRNA is a crucial regulatory stage in the pathway of gene expression. The majority of human genes that encode proteins undergo alternative pre-mRNA splicing and mutations that affect splicing are more prevalent than previously thought. Targeting aberrant RNA(s) may thus provide an opportunity to correct faulty splicing and potentially treat numerous genetic disorders. To that purpose, the use of engineered U1 snRNA (either modified U1 snRNAs or exon-specific U1s—ExSpeU1s) has been applied as a potentially therapeutic strategy to correct splicing mutations, particularly those affecting the 5′ splice-site (5′ss). Here we review and summarize a vast panoply of studies that used either modified U1 snRNAs or ExSpeU1s to mediate gene therapeutic correction of splicing defects underlying a considerable number of genetic diseases. We also focus on the pre-clinical validation of these therapeutic approaches both in vitro and in vivo, and summarize the main obstacles that need to be overcome to allow for their successful translation to clinic practice in the future. Full article
(This article belongs to the Special Issue Future Challenges and Trends of Nucleic Acids)
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19 pages, 1035 KiB  
Review
The Future of Point-of-Care Nucleic Acid Amplification Diagnostics after COVID-19: Time to Walk the Walk
by Juan García-Bernalt Diego, Pedro Fernández-Soto and Antonio Muro
Int. J. Mol. Sci. 2022, 23(22), 14110; https://doi.org/10.3390/ijms232214110 - 15 Nov 2022
Cited by 11 | Viewed by 3233
Abstract
Since the onset of the COVID-19 pandemic, over 610 million cases have been diagnosed and it has caused over 6.5 million deaths worldwide. The crisis has forced the scientific community to develop tools for disease control and management at a pace never seen [...] Read more.
Since the onset of the COVID-19 pandemic, over 610 million cases have been diagnosed and it has caused over 6.5 million deaths worldwide. The crisis has forced the scientific community to develop tools for disease control and management at a pace never seen before. The control of the pandemic heavily relies in the use of fast and accurate diagnostics, that allow testing at a large scale. The gold standard diagnosis of viral infections is the RT-qPCR. Although it provides consistent and reliable results, it is hampered by its limited throughput and technical requirements. Here, we discuss the main approaches to rapid and point-of-care diagnostics based on RT-qPCR and isothermal amplification diagnostics. We describe the main COVID-19 molecular diagnostic tests approved for self-testing at home or for point-of-care testing and compare the available options. We define the influence of specimen selection and processing, the clinical validation, result readout improvement strategies, the combination with CRISPR-based detection and the diagnostic challenge posed by SARS-CoV-2 variants for different isothermal amplification techniques, with a particular focus on LAMP and recombinase polymerase amplification (RPA). Finally, we try to shed light on the effect the improvement in molecular diagnostics during the COVID-19 pandemic could have in the future of other infectious diseases. Full article
(This article belongs to the Special Issue Future Challenges and Trends of Nucleic Acids)
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