scholarly journals Stability and Mismatch Discrimination of Locked Nucleic Acid–DNA Duplexes

Biochemistry ◽  
2011 ◽  
Vol 50 (43) ◽  
pp. 9352-9367 ◽  
Author(s):  
Richard Owczarzy ◽  
Yong You ◽  
Christopher L. Groth ◽  
Andrey V. Tataurov
Keyword(s):  
Nucleic Acid ◽  
Locked Nucleic Acid ◽  
Dna Duplexes ◽  
Mismatch Discrimination

Thermodynamic, Counterion, and Hydration Effects for the Incorporation of Locked Nucleic Acid Nucleotides into DNA Duplexes†

Biochemistry ◽  
2006 ◽  
Vol 45 (23) ◽  
pp. 7347-7355 ◽  
Author(s):  
Harleen Kaur ◽  
Amit Arora ◽  
Jesper Wengel ◽  
Souvik Maiti
Keyword(s):  
Nucleic Acid ◽  
Locked Nucleic Acid ◽  
Dna Duplexes

The effect of LNA nucleobases as enhancers for the binding of amiloride to an abasic site in DNA/DNA and DNA/RNA duplexes

2014 ◽  
Vol 12 (37) ◽  
pp. 7250-7256 ◽  
Author(s):  
Yusuke Sato ◽  
Tetsushi Sato ◽  
Takaya Sato ◽  
Seiichi Nishizawa ◽  
Norio Teramae
Keyword(s):  
Nucleic Acid ◽  
Locked Nucleic Acid ◽  
Dna Duplexes ◽  
Abasic Site ◽  
Rna Duplexes

We report on a significant effect of locked nucleic acid (LNA) nucleobases on the binding of amiloride for abasic site (AP)-containing DNA duplexes.

Splice-switching efficiency and specificity for oligonucleotides with locked nucleic acid monomers

2008 ◽  
Vol 412 (2) ◽  
pp. 307-313 ◽  
Author(s):  
Peter Guterstam ◽  
Maria Lindgren ◽  
Henrik Johansson ◽  
Ulf Tedebark ◽  
Jesper Wengel ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Antisense Oligonucleotides ◽  
High Efficiency ◽  
Locked Nucleic Acid ◽  
Switching Activity ◽  
Mismatch Discrimination ◽  
Therapeutic Platform ◽  
Splicing Patterns ◽  
Switching Efficiency ◽  
Target Effects

The use of antisense oligonucleotides to modulate splicing patterns has gained increasing attention as a therapeutic platform and, hence, the mechanisms of splice-switching oligonucleotides are of interest. Cells expressing luciferase pre-mRNA interrupted by an aberrantly spliced β-globin intron, HeLa pLuc705, were used to monitor the splice-switching activity of modified oligonucleotides by detection of the expression of functional luciferase. It was observed that phosphorothioate 2′-O-methyl RNA oligonucleotides containing locked nucleic acid monomers provide outstanding splice-switching activity. However, similar oligonucleotides with several mismatches do not impede splice-switching activity which indicates a risk for off-target effects. The splice-switching activity is abolished when mismatches are introduced at several positions with locked nucleic acid monomers suggesting that it is the locked nucleic acid monomers that give rise to low mismatch discrimination to target pre-mRNA. The results highlight the importance of rational sequence design to allow for high efficiency with simultaneous high mismatch discrimination for splice-switching oligonucleotides and suggest that splice-switching activity is tunable by utilizing locked nucleic acid monomers.

scholarly journals Modulating Anti-MicroRNA-21 Activity and Specificity Using Oligonucleotide Derivatives and Length Optimization

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Andrés Muñoz-Alarcón ◽  
Peter Guterstam ◽  
Cristian Romero ◽  
Mark A. Behlke ◽  
Kim A. Lennox ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Antisense Oligonucleotides ◽  
Posttranscriptional Regulation ◽  
Regulation Of Gene Expression ◽  
Locked Nucleic Acid ◽  
Cellular Functions ◽  
Mismatch Discrimination ◽  
Increased Activity ◽  
Length Optimization ◽  
Oligonucleotide Derivatives

MicroRNAs are short, endogenous RNAs that direct posttranscriptional regulation of gene expression vital for many developmental and cellular functions. Implicated in the pathogenesis of several human diseases, this group of RNAs provides interesting targets for therapeutic intervention. Anti-microRNA oligonucleotides constitute a class of synthetic antisense oligonucleotides used to interfere with microRNAs. In this study, we investigate the effects of chemical modifications and truncations on activity and specificity of anti-microRNA oligonucleotides targeting microRNA-21. We observed an increased activity but reduced specificity when incorporating locked nucleic acid monomers, whereas the opposite was observed when introducing unlocked nucleic acid monomers. Our data suggest that phosphorothioate anti-microRNA oligonucleotides yield a greater activity than their phosphodiester counterparts and that a moderate truncation of the anti-microRNA oligonucleotide improves specificity without significantly losing activity. These results provide useful insights for design of anti-microRNA oligonucleotides to achieve both high activity as well as efficient mismatch discrimination.

Maximizing Mismatch Discrimination by Surface-Tethered Locked Nucleic Acid Probes via Ionic Tuning

2013 ◽  
Vol 85 (3) ◽  
pp. 1615-1623 ◽  
Author(s):  
Sourav Mishra ◽  
Srabani Ghosh ◽  
Rupa Mukhopadhyay
Keyword(s):  
Nucleic Acid ◽  
Locked Nucleic Acid ◽  
Nucleic Acid Probes ◽  
Mismatch Discrimination

Trinucleotide Cap Analogue Bearing a Locked Nucleic Acid Moiety: Synthesis, mRNA Modification, and Translation for Therapeutic Applications

2021 ◽  
Author(s):  
Annamalai Senthilvelan ◽  
Tyson Vonderfecht ◽  
Muthian Shanmugasundaram ◽  
Indra Pal ◽  
Jason Potter ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Locked Nucleic Acid ◽  
Acid Moiety ◽  
Therapeutic Applications
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