[Progress in locked nucleic acid research].

Sheng Li Ke Xue Jin Zhan

Researsh Institute of Surgery, Third Military Medical University, Chongqing 400042.

Published: October 2003

Locked nucleic acid (LNA) is a novel oligonucleotide analogue in which 2'-O and 4'-C positions in the b-D-ribofuranosyl ring are joined via an O-methylene, S-methylene or amino-methylene moiety, locked in a C3'-endol3E north (N)-type furanose conformation. LNAs posses many properties, such as extraordinarily high hybridize affinities for complementary DNA/RNA sequences, remarkable antisense activity, nuclease resistance, good aqueous solubility and none detactable toxicity, et al. LNAs is a most promising molecule for development of diagnostics and therapeutics. For example, apply LNAs to single--nucleotide polymorphisms genotyping, telomerase activity have been efficiently suppressed by LNA oligomers, efficient cleavage of highly structured RNA has been achieved using LNA-modified DNAzymes (LNAzymes), and so on.

Download full-text PDF

Source

Publication Analysis

Top Keywords

locked nucleic
8
nucleic acid
8
[progress locked
4
acid research]
4
research] locked
4
acid lna
4
lna novel
4
novel oligonucleotide
4
oligonucleotide analogue
4
analogue 2'-o
4

Similar Publications

Anti-gene oligonucleotide clamps invade dsDNA and downregulate expression.

Mol Ther Nucleic Acids

December 2024

Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Alfred Nobels Allé 8, 14152 Huddinge, Stockholm, Sweden.

Anti-gene oligonucleotides belong to a group of therapeutic compounds, which, in contrast to antisense oligonucleotides, bind to DNA. Clamp anti-gene oligonucleotides bind through a double-stranded invasion mechanism. With two arms connected by a linker, they hybridize to one of the DNA strands forming Watson-Crick and Hoogsteen hydrogen bonds.

View Article and Find Full Text PDF

Introduction: Modification of natural enzymes to introduce new properties and enhance existing ones is a central challenge in bioengineering. This study is focused on the development of Taq polymerase mutants that show enhanced reverse transcriptase (RTase) activity while retaining other desirable properties such as fidelity, 5'- 3' exonuclease activity, effective deoxyuracyl incorporation, and tolerance to locked nucleic acid (LNA)-containing substrates. Our objective was to use AI-driven rational design combined with multiparametric wet-lab analysis to identify and validate Taq polymerase mutants with an optimal combination of these properties.

View Article and Find Full Text PDF

Unlabelled: Herpesviruses carry an assortment of proteins in the interstitial space between the capsid and membrane envelope, collectively referred to as the tegument. Upon virion fusion with a cell, envelope integrity is disrupted, and many tegument constituents disperse into the cytosol to carry out individual effector functions, while others direct transport of the capsid to the nucleus. To gain insight into the tegument dynamics that occur with disruption of envelope integrity, we used a combination of single-particle fluorescence and biochemical approaches that leveraged the previously established use of n-ethylmaleimide to inhibit virion dynamics.

View Article and Find Full Text PDF

We have subjected several analogs of DNA that have been widely used as antisense oligonucleotide (ASO) inhibitors of gene expression to comparative molecular dynamics (MD) calculations of their ability to form duplexes with DNA and RNA. The analogs included in this study are the phosphorothioate (PS), peptide nucleic acid (PNA), locked nucleic acid (LNA), morpholino nucleic acid (PMO), the 2'-OMe, 2'-F, 2'-methoxyethyl (2'-MOE) and the constrained cET analogs, as well as the natural phosphodiester (PO) as control, for a total of nine structures, in both XNA-DNA and XNA-RNA duplexes. This is intended as an objective criterion for their relative ability to duplex with an RNA complement and their comparative potential for antisense applications.

View Article and Find Full Text PDF

The design of controllable and precise RNA-targeted CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats) systems is an important problem of modern molecular biology and genetic technology. Herein, we have designed a series of photocleavable guide CRISPR RNAs (crRNA) and their 2'-modified (2'-fluoro and locked nucleic acid) analogs containing one or two 1-(2-nitrophenyl)-1,2-ethanediol photolabile linkers (PL). We have demonstrated that these crRNAs can be destroyed by relatively mild UVA irradiation with the rate constants 0.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!