Modified Oligonucleotides: Design, Synthesis and Application
A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Macromolecular Chemistry".
Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 3796
Special Issue Editor
2. Lead Researcher, Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Interests: nucleic acid chemistry; design of DNA and RNA analogues; oligonucleotide synthesis; modification and conjugation; oligonucleotide therapeutics; macromolecular drug delivery; DNA nanotechnology
Special Issue Information
Dear Colleagues,
Oligonucleotides, which by virtue of their intrinsic ability to recognize specific sequences of intracellular nucleic acids, primarily RNAs, through complementary base-pairing, are able to modulate their biological functions, have become an indispensable tool not only in molecular biology research but also in modern medicine as precision instruments for molecular diagnostics and therapy. As natural oligonucleotides are susceptible to enzymatic digestion when introduced into a living organism, the need for their stabilization through chemical modification is understood very early in their history. The first ever chemical modification—the phosphorothioate group that replaces one of the non-bridging oxygens of the phosphate group with sulfur—gave rise to the first generation of modified oligonucleotides that found application as enzymatically resistant phosphate mimetics and first oligonucleotide therapeutics. This has been followed by a plethora of other modifications: methyl phosphonates, 2’-O-alkyl RNAs, and bridged/locked nucleic acids (B/LNAs) to name just a few, involving every structural element of nucleic acids: nucleobase, sugar, and phosphate group or, sometimes, replacing all of these (save for nucleobases) with a non-natural framework such as peptide nucleic acids (PNAs) or phosphorodiamidate morpholino oligonucleotides (PMOs). One could argue that the golden age of exploring vast chemical modification space passed at the beginning of this millennium. Nevertheless, the two first decades of the 21st century have so far witnessed some particularly interesting developments in this field associated, in particular, with the discoveries of RNA interference (RNAi) and CRISPR/Cas9 genome editing, both now celebrated with Nobel prizes (2005 and 2020).
This Special Issue is aimed at providing a snapshot of contemporary modified oligonucleotide synthesis and applications, commemorating the 40th anniversary of the seminal paper by Beaucage and Caruthers that heralded the advent of the phosphoramidite chemistry (Tet. Let. 1981, 22, 1859–1862, doi:10.1016/S0040-4039(01)90461-7).
Dr. Dmitry A. Stetsenko
Guest Editor
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Keywords
- DNA and RNA analogues
- phosphate group mimics
- sugar-modified oligonucleotides
- base modifications
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