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Natural and Synthetic Modified Nucleic Acids: Their Properties, Functions and Applications

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

Deadline for manuscript submissions: 31 October 2025 | Viewed by 242

Special Issue Editor


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Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Sciences, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, Poland
Interests: therapeutic nucleic acids; siRNAs; antisense oligonucleotides; CRISPR/Cas9 gene editing; tRNA; epitranscriptomics; nucleoside modifications; nucleoside modifying enzymes; genetic code decoding; codon-anticodon interaction; oxidative tRNA damage; biotechnology and recombinant proteins
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Special Issue Information

Dear Colleagues,

A genetic system based on the nucleic acids DNA and RNA is a universal prerequisite for life and essential for the functioning of all living organisms. All natural nucleic acids contain chemically modified nucleosides in addition to the four canonical nucleosides (A,G,T/U,C). These modifications are defined and precisely introduced by specialized enzymes. DNA modifications, especially methylation, represent the epigenetic control of gene expression and play a fundamental role in many cellular processes. In addition, DNA methylation can be considered a hallmark of human diseases and can therefore be used as a potential biomarker. RNA molecules contain different types of post-transcriptional modifications that are responsible for modulating RNA function and gene expression. Thanks to increasingly modern techniques, mainly based on mass spectrometry and RNA sequencing, about 170 modified nucleosides have been identified in RNA, most of which concern transfer RNAs (tRNAs). Some RNA modifications are constant and conserved, while others are dynamic and reversible, occurring in rapid response to environmental changes. Despite the discovery of many types of modifications in RNA, new projects are being launched to identify all possible modifications, e.g., "The human RNome project". Another challenge is discovering the cellular pathways and enzymes responsible for the introduction or removal of nucleoside modifications in RNA, because our current knowledge of the enzymes that modify nucleosides in RNA is still incomplete.

In recent years, several cellular mechanisms have been discovered that allow the use of synthetic oligonucleotides for therapeutic purposes, mainly in the form of antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), aptamers, microRNAs, mRNAs and gene editing tools. Modified nucleotides are used in synthesis to improve the therapeutic properties of oligonucleotides, in particular stability in body fluids, prolongation of half-life and improvement of the process of delivery to cells.

We are pleased to invite you to a publication in this Special Issue of IJMS titled ‘Natural and Synthetic Modified Nucleic Acids: Their Properties, Functions and Applications’. The topic of this Special Issue is broad but focuses on the modifications of nucleosides found in natural nucleic acids DNA and RNA or intentionally introduced into synthetic oligonucleotides to increase stability, study interactions with other molecules, etc. We invite and encourage scientists to submit original research or review articles that address the latest aspects of research on nucleic acid modifications.

Dr. Malgorzata Sierant
Guest Editor

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Keywords

  • DNA
  • RNA
  • nucleic acid analogues
  • modified nucleosides
  • modified nucleosides identification techniques
  • nucleoside modifying enzymes
  • gene therapy
  • therapeutic nucleic acids
  • biomedical applications
  • drug delivery

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Published Papers (1 paper)

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Research

29 pages, 4988 KiB  
Article
Amphiphilic Oligonucleotide Derivatives as a Tool to Study DNA Repair Proteins
by Svetlana N. Khodyreva, Alexandra A. Yamskikh, Ekaterina S. Ilina, Mikhail M. Kutuzov, Ekaterina A. Belousova, Maxim S. Kupryushkin, Timofey D. Zharkov, Olga A. Koval, Sofia P. Zvereva and Olga I. Lavrik
Int. J. Mol. Sci. 2025, 26(15), 7078; https://doi.org/10.3390/ijms26157078 - 23 Jul 2025
Viewed by 143
Abstract
Modified oligonucleotides (oligos) are widely used as convenient tools in many scientific fields, including biomedical applications and therapies. In particular, oligos with lipophilic groups attached to the backbone ensure penetration of the cell membrane without the need for transfection. This study examines the [...] Read more.
Modified oligonucleotides (oligos) are widely used as convenient tools in many scientific fields, including biomedical applications and therapies. In particular, oligos with lipophilic groups attached to the backbone ensure penetration of the cell membrane without the need for transfection. This study examines the interaction between amphiphilic DNA duplexes, in which one of the chains contains a lipophilic substituent, and several DNA repair proteins, particularly DNA-damage-dependent PARPs, using various biochemical approaches. DNA with a lipophilic substituent (LS-DNA) demonstrates more efficient binding with DNA damage activated poly(AD-ribose) polymerases 1-3 (PARP1, PARP2, PARP3) and DNA polymerase β. Chemically reactive LS-DNA derivatives containing a photoactivatable nucleotide (photo-LS-DNAs) or a 5′ deoxyribose phosphate (dRP) group in the vicinity of double-strand breaks (DSBs) are used for the affinity labelling of PARPs and other proteins in several whole-cell extracts of human cells. In particular, photo-LS-DNAs are used to track the level of Ku antigen in the extracts of neuron-like differentiated SH-SY5Y, undifferentiated SH-SY5Y, and olfactory epithelial cells. In vitro, PARP1–PARP3 are shown to be able to slowly excise the 5′ dRP group at DSBs. LS-DNAs can activate PARP1 and PARP2 for autoPARylation, albeit less effectively than regular DNA duplexes. Full article
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