Locked nucleic acids (LNAs) are novel base modifications containing a methylene bridge uniting the 2'-oxygen and the 4'-carbon. In this study, LNA-modified single-stranded molecules directed the repair of single base mutations in a yeast chromosomal gene. Using a genetic assay involving a mutant hygromycin-resistance gene, correction of point and frameshift mutations was facilitated by vectors containing an LNA residue on each terminus. Increasing the number of LNA bases on each terminus reduced the correction frequency progressively. When the LNA vector is used in combination with a phosphorothioate-modified vector (74-mer), however, a high level of gene-repair activity occurs; hence, short LNA-based vectors can augment the activity of other types of targeting vectors. These data suggest that oligonucleotides containing locked nucleic acid residues can be used to direct single nucleotide exchange reactions in vivo.
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http://dx.doi.org/10.1016/s1074-5521(02)00236-3 | DOI Listing |
Mol Ther Nucleic Acids
March 2025
Department of Molecular Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.
Currently, no drugs directly treat liver fibrosis. Previously, we have shown that treatment with miR-29a-3p improved liver fibrosis in a mouse model. To investigate the effectiveness of nucleic acid therapy at a lower dose, a modified nucleic acid was prepared based on miR-29a-3p.
View Article and Find Full Text PDFAnal Chem
January 2025
State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, P. R. China.
Despite the unique advantage of the isothermal exponential amplification reaction (EXPAR) for the rapid detection of short nucleic acids, it severely suffers from the drawback of sequence-dependent amplification bias, mainly arising from the secondary structures of the EXPAR template under the commonly used reaction temperature (55 °C). As such, the limits of detection (LOD) for different target sequences may vary considerably from aM to nM. Here we report a sequence-generic exponential amplification reaction (SG-EXPAR) that eliminates sequence-dependent amplification bias and achieves similar amplification performance for different targets with generally sub-fM LODs.
View Article and Find Full Text PDFJ Microbiol Methods
January 2025
Charlottetown Research and Development Centre, Agriculture and Agri-Food Canada, 440 University Avenue, Charlottetown, PE C1A 4N6, Canada. Electronic address:
The devastating plant pathogen Fusarium graminearum produces mycotoxins including the novel 3ANX toxin. To detect 3ANX-producing isolates, SYBR Green and locked nucleic acid probe assays were developed, targeting 3ANX Tri1 polymorphisms. Assays were efficient with R > 0.
View Article and Find Full Text PDFEpigenetics Chromatin
January 2025
Clinical Big Data Research Center, Scientific Research Center, Shenzhen Key Laboratory of Bone Tissue Repair and Translational Research, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, 518107, People's Republic of China.
Background: Histone modification H3K27me3 plays a critical role in normal development and is associated with various diseases, including cancer. This modification forms large chromatin domains, known as Large Organized Chromatin Lysine Domains (LOCKs), which span several hundred kilobases.
Result: In this study, we identify and categorize H3K27me3 LOCKs in 109 normal human samples, distinguishing between long and short LOCKs.
Nature
January 2025
Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China.
Argonaute proteins are categorized into AGO and PIWI clades. Across most animal species, AGO-clade proteins are widely expressed in various cell types, and regulate normal gene expression. By contrast, PIWI-clade proteins predominantly function during gametogenesis to suppress transposons and ensure fertility.
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