Gapmer Antisense Oligonucleotides Containing 2′,3′‐Dideoxy‐2′‐fluoro‐3′‐ C ‐hydroxymethyl‐β‐ d ‐lyxofuranosyl Nucleotides Display Site‐Specific RNase H Cleavage and Induce Gene Silencing

2020 ◽  
Vol 26 (6) ◽  
pp. 1368-1379
Author(s):  
Mathias B. Danielsen ◽  
Chenguang Lou ◽  
Jolanta Lisowiec‐Wachnicka ◽  
Anna Pasternak ◽  
Per T. Jørgensen ◽  
...  
RSC Advances ◽  
2016 ◽  
Vol 6 (96) ◽  
pp. 93398-93402 ◽  
Author(s):  
Xingyu Wang ◽  
Xingguo Liang

Photoresponsive azobenzene-modified antisense oligonucleotides for site-specific RNA cleavage by RNase H.


2008 ◽  
Vol 86 (7) ◽  
pp. 641-656 ◽  
Author(s):  
Jonathan K Watts ◽  
Masad J Damha

The development of arabinonucleosides and oligoarabinonucleotides is described, focusing especially on 2′-deoxy-2′-fluoroarabinonucleosides (araF-N) and -oligonucleotides (2'F-ANA). In addition to their chemical and enzymatic synthesis, we discuss various properties of 2′F-ANA: hydrolytic stability (to nucleases, acids, and bases), binding affinity to complementary strands, structure and conformation, and optimization of RNase H activity. We also discuss the use of 2′F-ANA in gene-silencing approaches (antisense, siRNA), and in the stabilization of higher-order structures (such as triplexes and quadruplexes) including aptamers. Finally, we examine several other oligonucleotide derivatives based on 2′F-ANA and look ahead to the future of 2′-fluoroarabinonucleosides and -oligonucleotides.Key words: arabinonucleic acids, 2′F-ANA, antisense oligonucleotides, siRNA, modified oligonucleotides.


Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 416
Author(s):  
Saumya Jani ◽  
Maria Soledad Ramirez ◽  
Marcelo E. Tolmasky

Antisense technologies consist of the utilization of oligonucleotides or oligonucleotide analogs to interfere with undesirable biological processes, commonly through inhibition of expression of selected genes. This field holds a lot of promise for the treatment of a very diverse group of diseases including viral and bacterial infections, genetic disorders, and cancer. To date, drugs approved for utilization in clinics or in clinical trials target diseases other than bacterial infections. Although several groups and companies are working on different strategies, the application of antisense technologies to prokaryotes still lags with respect to those that target other human diseases. In those cases where the focus is on bacterial pathogens, a subset of the research is dedicated to produce antisense compounds that silence or reduce expression of antibiotic resistance genes. Therefore, these compounds will be adjuvants administered with the antibiotic to which they reduce resistance levels. A varied group of oligonucleotide analogs like phosphorothioate or phosphorodiamidate morpholino residues, as well as peptide nucleic acids, locked nucleic acids and bridge nucleic acids, the latter two in gapmer configuration, have been utilized to reduce resistance levels. The major mechanisms of inhibition include eliciting cleavage of the target mRNA by the host’s RNase H or RNase P, and steric hindrance. The different approaches targeting resistance to β-lactams include carbapenems, aminoglycosides, chloramphenicol, macrolides, and fluoroquinolones. The purpose of this short review is to summarize the attempts to develop antisense compounds that inhibit expression of resistance to antibiotics.


2017 ◽  
Vol 27 (4) ◽  
pp. 232-237 ◽  
Author(s):  
Mado Nakajima ◽  
Takeshi Kasuya ◽  
Shinnichi Yokota ◽  
Reina Onishi ◽  
Tatsuya Ikehara ◽  
...  

1996 ◽  
Vol 24 (4) ◽  
pp. 760-765 ◽  
Author(s):  
M. A. Reynolds ◽  
T. A. Beck ◽  
P. B. Say ◽  
D. A. Schwartz ◽  
B. P. Dwyer ◽  
...  

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