Investigation of twisted intercalating nucleic acid (TINA)-modified antisense oligonucleotides for splice modulation by induced exon-skipping in vitro

RSC Advances ◽  
2016 ◽  
Vol 6 (97) ◽  
pp. 95169-95172 ◽  
Author(s):  
Bao T. Le ◽  
Vyacheslav V. Filichev ◽  
Rakesh N. Veedu
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Antisense Oligonucleotides ◽  
Exon Skipping

We have investigated the applicability of twisted intercalating nucleic acids (TINA)-modified antisense oligonucleotides (AOs) in exon skipping. We found that TINA-modified AOs induced exon skipping.

scholarly journals Alpha-l-Locked Nucleic Acid-Modified Antisense Oligonucleotides Induce Efficient Splice Modulation In Vitro

2020 ◽  
Vol 21 (7) ◽  
pp. 2434
Author(s):  
Prithi Raguraman ◽  
Tao Wang ◽  
Lixia Ma ◽  
Per Trolle Jørgensen ◽  
Jesper Wengel ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Antisense Oligonucleotides ◽  
Exon Skipping ◽  
Initial Study ◽  
Locked Nucleic Acid ◽  
Mdx Mouse ◽  
Complementary Oligonucleotide ◽  
Low Cytotoxicity ◽  
Target Binding

Alpha-l-Locked nucleic acid (α-l-LNA) is a stereoisomeric analogue of locked nucleic acid (LNA), which possesses excellent biophysical properties and also exhibits high target binding affinity to complementary oligonucleotide sequences and resistance to nuclease degradations. Therefore, α-l-LNA nucleotides could be utilised to develop stable antisense oligonucleotides (AO), which can be truncated without compromising the integrity and efficacy of the AO. In this study, we explored the potential of α-l-LNA nucleotides-modified antisense oligonucleotides to modulate splicing by inducing Dmd exon-23 skipping in mdx mouse myoblasts in vitro. For this purpose, we have synthesised and systematically evaluated the efficacy of α-l-LNA-modified 2′-O-methyl phosphorothioate (2′-OMePS) AOs of three different sizes including 20mer, 18mer and 16mer AOs in parallel to fully-modified 2′-OMePS control AOs. Our results demonstrated that the 18mer and 16mer truncated AO variants showed slightly better exon-skipping efficacy when compared with the fully-23 modified 2′-OMePS control AOs, in addition to showing low cytotoxicity. As there was no previous report on using α-l-LNA-modified AOs in splice modulation, we firmly believe that this initial study could be beneficial to further explore and expand the scope of α-l-LNA-modified AO therapeutic molecules.

Evaluation of anhydrohexitol nucleic acid, cyclohexenyl nucleic acid andd-altritol nucleic acid-modified 2′-O-methyl RNA mixmer antisense oligonucleotides for exon skipping in vitro

2016 ◽  
Vol 52 (92) ◽  
pp. 13467-13470 ◽  
Author(s):  
Bao T. Le ◽  
Suxiang Chen ◽  
Mikhail Abramov ◽  
Piet Herdewijn ◽  
Rakesh N. Veedu
Keyword(s):  
Nucleic Acid ◽  
Antisense Oligonucleotides ◽  
Exon Skipping ◽  
Antisense Oligos

We have investigated the potential of anhydrohexitol, cyclohexenyl and altritol nucleic acid-modified antisense oligos in exon skipping, and found that they efficiently inducedDmdexon 23 skipping.

In vitro evaluation of hexitol nucleic acid antisense oligonucleotides

1999 ◽  
Author(s):  
Arthur Van Aerschot ◽  
Mark Vandermeeren ◽  
Johan Geysen ◽  
Walter Luyten ◽  
Marc Miller ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Antisense Oligonucleotides ◽  
In Vitro Evaluation

scholarly journals Quantitative Evaluation of Nucleic Acid Degradability of Copper Alloy Surfaces and Its Correlation to Antibacterial Activity

Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1439
Author(s):  
Akiko Yamamoto ◽  
Shinji Tanaka ◽  
Keiichiro Ohishi
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Copper Ion ◽  
Antibacterial Activities ◽  
Ion Release ◽  
Antibacterial Materials ◽  
Cu Content ◽  
Cu Alloys ◽  
Film Method

Copper (Cu) and its alloys have bactericidal activity known as “contact killing” with degradation of nucleic acids inside the bacteria, which is beneficial to inhibit horizontal gene transfer (HGF). In order to understand the nucleic acid degradability of Cu and its alloy surfaces, we developed a new in vitro method to quantitatively evaluate it by a swab method under a “dry” condition and compared it with that of commercially available antibacterial materials such as antibacterial stainless steel, pure silver, and antibacterial resins. As a result, only Cu and its alloys showed continuous degradation of nucleic acids for up to 6 h of contact time. The nucleic acid degradability levels of the Cu alloys and other antibacterial materials correlate to their antibacterial activities evaluated by a film method referring to JIS Z 2801:2012 for Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria. Nucleic acid degradation by copper (I) and (II) chlorides was confirmed at the ranges over 10 mM and 1–20 mM, respectively, suggesting that the copper ion release may be responsible for the degradation of the nucleic acids on Cu and its alloy surfaces. In conclusion, the higher Cu content in the alloys gave higher nucleic acid degradability and higher antibacterial activities.

Insulin and incorporation of radioactivity into nucleic acid fraction of isolated diaphragm

1960 ◽  
Vol 199 (4) ◽  
pp. 719-721 ◽  
Author(s):  
Ira G. Wool
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Glucose Concentration ◽  
Orotic Acid ◽  
Acid Fraction ◽  
Rat Diaphragm ◽  
Isolated Rat

Insulin in vitro stimulated the incorporation into the nucleic acid fraction of isolated rat diaphragm of radioactivity from d-glucose-U-C14, adenine-8-C14 and orotic acid-6-C14; insulin had no effect on the incorporation of thymine-2-C14 into muscle nucleic acids. Insulin enhanced the incorporation into nucleic acids of C14 from adenine and orotic acid in the absence of added glucose, and incorporation of adenine-8-C14 was not influenced by glucose concentration over the range 0–600 mg %.

scholarly journals Nucleobase-modified antisense oligonucleotides containing 5-(phenyltriazol)-2′-deoxyuridine nucleotides induce exon-skipping in vitro

RSC Advances ◽  
2017 ◽  
Vol 7 (86) ◽  
pp. 54542-54545 ◽  
Author(s):  
Bao T. Le ◽  
Mick Hornum ◽  
Pawan K. Sharma ◽  
Poul Nielsen ◽  
Rakesh N. Veedu
Keyword(s):  
Antisense Oligonucleotides ◽  
Exon Skipping

We investigated the potential of nucleobase-modified antisense oligonucleotides to induce exon-skipping, and found that 5-(phenyltriazol)-2′-deoxyuridine-modified antisense oligonucleotides induced efficient exon-skipping in vitro.

Hydroxyproline-Based DNA Mimics: A Review on Synthesis and Properties

2006 ◽  
Vol 71 (7) ◽  
pp. 929-955 ◽  
Author(s):  
Vladimir A. Efimov ◽  
Oksana G. Chakhmakhcheva
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Phosphonic Acid ◽  
Peptide Nucleic Acids ◽  
Biological Properties ◽  
High Potential ◽  
Physicochemical And Biological Properties

With the aim to improve physicochemical and biological properties of natural oligonucleotides, many types of DNA analogues and mimics are designed on the basis of hydroxyproline and its derivatives, and their properties are evaluated. Among them, two types of DNA mimics representing hetero-oligomers constructed from alternating monomers of phosphono peptide nucleic acids and monomers on the base of trans-1-acetyl-4-hydroxy-L-proline (HypNA-pPNAs) and oligomers constructed from monomers containing (2S,4R)-1-acetyl-4-hydroxypyrrolidine-2-phosphonic acid backbone (pHypNAs) are of particular interest. In a set of in vitro and in vivo assays, it was shown that HypNA-pPNAs and pHypNAs demonstrated a high potential for the use in nucleic acid based diagnostics, isolation of nucleic acids and antisense experiments. A review with 53 references.

Sign in / Sign up

Export Citation Format

Share Document