Oligonucleotide-based gene silencing, using molecules such as antisense oligonucleotides (ASOs), small interfering RNA, and aptamers, is widely studied. Another approach uses DNA/RNA heteroduplex oligonucleotides (HDOs). Here, we developed an antisense double-stranded DNA oligonucleotide (ADO) by modification of the complementary RNA in an HDO to generate DNA for increasing resistance to nucleases. Naked BCR-ABL-targeting ADO was significantly more potent than siRNA at reducing BCR-ABL chimeric mRNA expression in chronic myeloid leukemia (CML) cell lines. Further, naked BCR-ABL-targeting ADO suppressed BCR-ABL protein levels in a dose-dependent manner, inhibited CML cell proliferation, and augmented the inhibitory effects of imatinib mesylate. In conclusion, ADO technology is an attractive method for therapeutic application.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s10637-019-00862-9 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Previous RNA profiling studies revealed co-expression of overlapping sense/antisense (s/a) transcripts in pro- and eukaryotic organisms. Functional analyses in yeast have shown that certain s/a mRNA/mRNA and mRNA/lncRNA pairs form stable double-stranded RNAs (dsRNAs) that affect transcript stability. Little is known, however, about the genome-wide prevalence of dsRNA formation and its potential functional implications during growth and development in diploid budding yeast.
View Article and Find Full Text PDFIdentification of Antisense RNA NRAS-AS and Its Preliminary Exploration of the Anticancer Regulatory Mechanism.
Genes (Basel)
November 2024
College of Animal Science and Technology, Institute of Epigenetics and Epigenomics, Yangzhou University, Yangzhou 225001, China.
Objective: To explore the influence of NRAS-AS on the proliferation, apoptosis, cell cycle, migration, and invasion ability of HCC cells, as well as its underlying mechanisms.
Methods: A double-stranded cDNA library for liver cancer cells was constructed, and identified NRAS-AS through High-throughput sequencing, bioinformatics, chain-specific fluorescent quantitative PCR, and RACE. NRAS-AS's effects on HepG2 and SMMC-7721 cells and gene expression were evaluated.
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 PDFAsymmetric distribution of G-quadruplex forming sequences in genomes of retroviruses.
Sci Rep
January 2025
Institute of Biophysics, Czech Academy of Sciences , Královopolská 135, Brno, 612 65, Czech Republic.
Retroviruses are among the most extensively studied viral families, both historically and in contemporary research. They are primarily investigated in the fields of viral oncogenesis, reverse transcription mechanisms, and other infection-specific aspects. These include the integration of endogenous retroviruses (ERVs) into host genomes, a process widely utilized in genetic engineering, and the ongoing search for HIV/AIDS treatment.
View Article and Find Full Text PDFMultispanning membrane protein SIDT2 increases knockdown activity of gapmer antisense oligonucleotides.
Sci Rep
January 2025
Osaka Medical and Pharmaceutical University, 4-20-1, Nasahara, Takatsuki, 569-1094, Osaka, Japan.
Recent advances in the clinical development of oligonucleotide therapeutics, such as antisense oligonucleotides (ASOs) and small interfering RNAs, have attracted attention as promising therapeutic modalities for genetic and intractable diseases. These oligonucleotide therapeutics exert their efficacy by binding to target RNAs present within cells; however, the mechanisms underlying their cellular uptake, especially their passage through membranes, remain largely unclear. In the nematode, Caenorhabditis elegans, the multi-pass transmembrane protein, SID-1, is involved in the cellular uptake of double-stranded RNAs.
View Article and Find Full Text PDFWant 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!