Abstract
Oligonucleotides are key compounds widely used for research, diagnostics, and therapeutics. The rapid increase in oligonucleotide-based applications, together with the progress in nucleic acids research, has led to the design of nucleotide analogs that, when part of these oligomers, enhance their efficiency, bioavailability, or stability. One of the most useful nucleotide analogs is the first-generation bridged nucleic acids (BNA), also known as locked nucleic acids (LNA), which were used in combination with ribonucleotides, deoxyribonucleotides, or other analogs to construct oligomers with diverse applications. However, there is still room to improve their efficiency, bioavailability, stability, and, importantly, toxicity. A second-generation BNA, BNANC (2′-O,4′-aminoethylene bridged nucleic acid), has been recently made available. Oligomers containing these analogs not only showed less toxicity when compared to LNA-containing compounds but, in some cases, also exhibited higher specificity. Although there are still few applications where BNANC-containing compounds have been researched, the promising results warrant more effort in incorporating these analogs for other applications. Furthermore, newer BNA compounds will be introduced in the near future, offering great hope to oligonucleotide-based fields of research and applications.
Highlights
The rapid increase in oligonucleotide-based applications, together with the progress in nucleic acids research, has led to the design of nucleotide analogs that, when part of these oligomers, enhance their efficiency, bioavailability, or stability
Several approaches were attempted to reduce the undesirable expression of genes, utilizing a variety of strategies, the vast majority of which have in common the utilization of antisense oligonucleotides [1,2,3]
The values were higher for oligonucleotides substituted with BNANC than those that included locked nucleic acids (LNA) residues [29]. These results indicate that BNANC residues conferred a higher RNA selective binding affinity to the antisense oligomers
Summary
Oligonucleotides are short oligomers composed of ribonucleotides or deoxyribonucleotides. Several approaches were attempted to reduce the undesirable expression of genes, utilizing a variety of strategies, the vast majority of which have in common the utilization of antisense oligonucleotides [1,2,3] Many of these compounds are known with different names descriptive of their mechanism of action, like external guide sequences [4,5], ribozymes [6,7], aptamers [8,9], short interfering RNA [10,11,12], and microRNA [13,14]. 1) or making more drastic structural changes the replacing drastic changes replacing or modifying the ribose, substituting natureor ofmodifying the bonds,the or ribose, substituting the nature of the bonds, or modifying the charge of the oligonucleotide, obtaining modifying the charge of the oligonucleotide, obtaining neutral or cationic derivatives. This review will focus on the properties and applications of BNA applications of BNA -containing compounds
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