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Advanced Research on Nucleic Acids: Therapeutic Potential and Applications, 2nd Edition

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

Deadline for manuscript submissions: 20 February 2025 | Viewed by 4855

Special Issue Editors

Dr. Veronica Esposito

E-Mail Website
Guest Editor
Department of Pharmacy, Università degli Studi di Napoli Federico II, 80131 Naples, Italy
Interests: G-quadruplex; aptamers; nucleic acid chemistry; nuclear magnetic resonance; electrophoretic tecniques; circular dichroism; G4-catalysts
Special Issues, Collections and Topics in MDPI journals
Dr. Antonella Virgilio

E-Mail Website
Guest Editor
Department of Pharmacy, Università degli Studi di Napoli Federico II, 80131 Naples, Italy
Interests: G-quadruplex; aptamers; nucleic acid chemistry; circular dichroism; electrophoresis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue, entitled “Advanced Research on Nucleic Acids: Therapeutic Potential and Applications”, will present a selection of original research, reviews, and commentaries focused on diverse topics in this field, with particular attention being paid to advancements in nucleic acid research at the molecular level. Nucleic acid therapeutics represent an innovative and challenging research field. Oligonucleotide (ON)-based therapy has become an alternative to classical approaches in the search for novel therapeutics involving gene-related diseases. Nucleic-acid-based drugs can be designed to modulate cellular pathways that are not readily druggable, and different nucleic acid chemical modifications can be optimally combined in the context of various targeting mechanisms, in order to circumvent the main pharmacokinetic restrictions for therapeutic ON applications. The wide versatility of the mechanism of action of ONs, combined with various designs and multiple choices of chemical modifications, provide the concept of ON targeting with vast potential. Clinically relevant applications and remaining challenges in this field are still numerous and exciting.

Dr. Veronica Esposito
Dr. Antonella Virgilio
Guest Editors

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Keywords

  • aptamer
  • decoy
  • DNAzyme
  • ribozyme
  • siRNA
  • miRNA
  • antisense oligonucleotide
  • antigene strategy
  • G-quadruplex
  • triplex

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Related Special Issue

Published Papers (4 papers)

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Research

16 pages, 2188 KiB  
Article
Probing the Effects of Chemical Modifications on Anticoagulant and Antiproliferative Activity of Thrombin Binding Aptamer
by Antonella Virgilio, Daniela Benigno, Carla Aliberti, Ivana Bello, Elisabetta Panza, Martina Smimmo, Valentina Vellecco, Veronica Esposito and Aldo Galeone
Int. J. Mol. Sci. 2025, 26(1), 134; https://doi.org/10.3390/ijms26010134 - 27 Dec 2024
Viewed by 524
Abstract
Thrombin binding aptamer (TBA) is one of the best-known G-quadruplex (G4)-forming aptamers that efficiently binds to thrombin, resulting in anticoagulant effects. TBA also possesses promising antiproliferative properties. As with most therapeutic oligonucleotides, chemical modifications are critical for therapeutic applications, particularly to improve thermodynamic [...] Read more.
Thrombin binding aptamer (TBA) is one of the best-known G-quadruplex (G4)-forming aptamers that efficiently binds to thrombin, resulting in anticoagulant effects. TBA also possesses promising antiproliferative properties. As with most therapeutic oligonucleotides, chemical modifications are critical for therapeutic applications, particularly to improve thermodynamic stability, resistance in biological environment, and target affinity. To evaluate the effects of nucleobase and/or sugar moiety chemical modifications, five TBA analogues have been designed and synthesized considering that the chair-like G4 structure is crucial for biological activity. Their structural and biological properties have been investigated by Circular Dichroism (CD), Nuclear Magnetic Resonance (NMR), native polyacrylamide gel electrophoresis (PAGE) techniques, and PT and MTT assays. The analogue TBAB contains 8-bromo-2′-deoxyguanosine (B) in G-syn glycosidic positions, while TBAL and TBAM contain locked nucleic acid guanosine (L) or 2′-O-methylguanosine (M) in G-anti positions, respectively. Instead, both the two types of modifications have been introduced in TBABL and TBABM with the aim of obtaining synergistic effects. In fact, both derivatives include B in syn positions, exhibiting in turn L and M in the anti ones. The most appealing results have been obtained for TBABM, which revealed an interesting cytotoxic activity against breast and prostate cancer cell lines, while in the case of TBAB, extraordinary thermal stability (Tm approximately 30 °C higher than that of TBA) and an anticoagulant activity higher than original aptamer were observed, as expected. These data indicate TBAB as the best TBA anticoagulant analogue here investigated and TBABM as a promising antiproliferative derivative. Full article
(This article belongs to the Special Issue Advanced Research on Nucleic Acids: Therapeutic Potential and Applications, 2nd Edition)
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16 pages, 3290 KiB  
Article
A Surface-Enhanced Raman Spectroscopy-Based Aptasensor for the Detection of Deoxynivalenol and T-2 Mycotoxins
by Rugiya Alieva, Svetlana Sokolova, Natalia Zhemchuzhina, Dmitrii Pankin, Anastasia Povolotckaia, Vasiliy Novikov, Sergey Kuznetsov, Anatoly Gulyaev, Maksim Moskovskiy and Elena Zavyalova
Int. J. Mol. Sci. 2024, 25(17), 9534; https://doi.org/10.3390/ijms25179534 - 2 Sep 2024
Viewed by 1006
Abstract
The quality of food is one of the emergent points worldwide. Many microorganisms produce toxins that are harmful for human and animal health. In particular, mycotoxins from Fusarium fungi are strictly controlled in cereals. Simple and robust biosensors are necessary for ‘in field’ [...] Read more.
The quality of food is one of the emergent points worldwide. Many microorganisms produce toxins that are harmful for human and animal health. In particular, mycotoxins from Fusarium fungi are strictly controlled in cereals. Simple and robust biosensors are necessary for ‘in field’ control of the crops and processed products. Nucleic acid-based sensors (aptasensors) offer a new era of point-of-care devices with excellent stability and limits of detection for a variety of analytes. Here we report the development of a surface-enhanced Raman spectroscopy (SERS)-based aptasensor for the detection of T-2 and deoxynivalenol in wheat grains. The aptasensor was able to detect as low as 0.17% of pathogen fungi in the wheat grains. The portable devices, inexpensive SERS substrate, and short analysis time encourage further implementation of the aptasensors outside of highly equipped laboratories. Full article
(This article belongs to the Special Issue Advanced Research on Nucleic Acids: Therapeutic Potential and Applications, 2nd Edition)
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15 pages, 4120 KiB  
Article
Circular RNA Profile in Atherosclerotic Disease: Regulation during ST-Elevated Myocardial Infarction
by Fredric A. Holme, Camilla Huse, Xiang Yi Kong, Kaspar Broch, Lars Gullestad, Anne Kristine Anstensrud, Geir Ø. Andersen, Brage H. Amundsen, Ola Kleveland, Ana Quiles-Jimenez, Sverre Holm, Pål Aukrust, Ingrun Alseth, Bente Halvorsen and Tuva B. Dahl
Int. J. Mol. Sci. 2024, 25(16), 9014; https://doi.org/10.3390/ijms25169014 - 19 Aug 2024
Viewed by 1482
Abstract
Circular (circ) RNAs are non-coding RNAs with important functions in the nervous system, cardiovascular system, and cancer. Their role in atherosclerosis and myocardial infarction (MI) remains poorly described. We aim to investigate the potential circRNAs in immune cells during atherogenesis and examine the [...] Read more.
Circular (circ) RNAs are non-coding RNAs with important functions in the nervous system, cardiovascular system, and cancer. Their role in atherosclerosis and myocardial infarction (MI) remains poorly described. We aim to investigate the potential circRNAs in immune cells during atherogenesis and examine the most regulated during MI and the modulation by interleukin (IL)-6 receptor inhibition by tocilizumab. Wild-type (WT) and ApoE−/− mice were fed an atherogenic diet for 10 weeks, and the circRNA profile was analyzed by circRNA microarray. Whole blood from patients with ST-elevated MI (STEMI) and randomized to tocilizumab (n = 21) or placebo (n = 19) was collected at admission, 3–7 days, and at 6 months, in addition to samples from healthy controls (n = 13). Primers for human circRNA were designed, and circRNA levels were measured using RT-qPCR. mRNA regulation of predicted circRNA targets was investigated by RNA sequencing. The expression of 867 circRNAs differed between atherogenic and WT mice. In STEMI patients, circUBAC2 was significantly lower than in healthy controls. CircANKRD42 and circUBAC2 levels were inversely correlated with troponin T, and for circUBAC2, an inverse correlation was also seen with final infarct size at 6 months. The predicted mRNA targets for circUBAC2 and circANKRD42 were investigated and altered levels of transcripts involved in the regulation of inflammatory/immune cells, apoptosis, and mitochondrial function were found. Finally, tocilizumab induced an up-regulation of circANKRD42 and circUBAC2 3–7 days after percutaneous coronary intervention. CircRNA levels were dysregulated in STEMI, potentially influencing the immune system, apoptosis, and mitochondrial function. Full article
(This article belongs to the Special Issue Advanced Research on Nucleic Acids: Therapeutic Potential and Applications, 2nd Edition)
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15 pages, 2800 KiB  
Article
DNA Aptamer Raised against Advanced Glycation End Products Improves Sperm Concentration, Motility, and Viability by Suppressing Receptors for Advanced Glycation End Product-Induced Oxidative Stress and Inflammation in the Testes of Diabetic Mice
by Yusaku Mori, Michishige Terasaki, Naoya Osaka, Tomoki Fujikawa, Hironori Yashima, Tomomi Saito, Yurie Kataoka, Makoto Ohara, Yuichiro Higashimoto, Takanori Matsui and Sho-ichi Yamagishi
Int. J. Mol. Sci. 2024, 25(11), 5947; https://doi.org/10.3390/ijms25115947 - 29 May 2024
Cited by 4 | Viewed by 1213
Abstract
Type 2 diabetes mellitus (T2DM) is a risk factor for male infertility, but the underlying molecular mechanisms remain unclear. Advanced glycation end products (AGEs) are pathogenic molecules for diabetic vascular complications. Here, we investigated the effects of the DNA aptamer raised against AGEs [...] Read more.
Type 2 diabetes mellitus (T2DM) is a risk factor for male infertility, but the underlying molecular mechanisms remain unclear. Advanced glycation end products (AGEs) are pathogenic molecules for diabetic vascular complications. Here, we investigated the effects of the DNA aptamer raised against AGEs (AGE-Apt) on testicular and sperm abnormalities in a T2DM mouse model. KK-Ay (DM) and wild-type (non-DM) 4- and 7-week-old male mice were sacrificed to collect the testes and spermatozoa for immunofluorescence, RT-PCR, and histological analyses. DM and non-DM 7-week-old mice were subcutaneously infused with the AGE-Apt or control-aptamer for 6 weeks and were then sacrificed. Plasma glucose, testicular AGEs, and Rage gene expression in 4-week-old DM mice and plasma glucose, testicular AGEs, oxidative stress, and pro-inflammatory gene expressions in 7-week-old DM mice were higher than those in age-matched non-DM mice, the latter of which was associated with seminiferous tubular dilation. AGE-Apt did not affect glycemic parameters, but it inhibited seminiferous tubular dilation, reduced the number of testicular macrophages and apoptotic cells, and restored the decrease in sperm concentration, motility, and viability of 13-week-old DM mice. Our findings suggest that AGEs-Apt may improve sperm abnormality by suppressing AGE–RAGE-induced oxidative stress and inflammation in the testes of DM mice. Full article
(This article belongs to the Special Issue Advanced Research on Nucleic Acids: Therapeutic Potential and Applications, 2nd Edition)
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