Triplex-forming oligonucleotide target sequences in the human genome.

Nucleic Acids Res

Molecular Modelling and Bioinformatics Unit, Institut de Recerca Biomédica, Parc Científic de Barcelona, Josep Samitier 1-5, Barcelona 08028, Spain.

Published: February 2004

The existence of sequences in the human genome which can be a target for triplex formation, and accordingly are candidates for anti-gene therapies, has been studied by using bioinformatics tools. It was found that the population of triplex-forming oligonucleotide target sequences (TTS) is much more abundant than that expected from simple random models. The population of TTS is large in all the genome, without major differences between chromosomes. A wide analysis along annotated regions of the genome allows us to demonstrate that the largest relative concentration of TTS is found in regulatory regions, especially in promoter zones, which suggests a tremendous potentiality for triplex strategy in the control of gene expression. The dependence of the stability and selectivity of the triplexes on the length of the TTS is also analysed using knowledge-based rules.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC373298PMC
http://dx.doi.org/10.1093/nar/gkh188DOI Listing

Publication Analysis

Top Keywords

triplex-forming oligonucleotide
8
oligonucleotide target
8
target sequences
8
sequences human
8
human genome
8
genome
4
genome existence
4
existence sequences
4
genome target
4
target triplex
4

Similar Publications

Psoralen-conjugated triplex-forming oligonucleotides (Ps-TFOs) have been employed for the photodynamic regulation of gene expression by the photo-cross-linking of psoralen with the target DNA. However, stable triplex formation requires a consecutive purine base sequence in one strand of the target DNA duplexes. The pyrimidine-base interruption in the consecutive purine base sequence drastically decreases the thermodynamic stability of the corresponding triplex, which hampers the TFO application.

View Article and Find Full Text PDF

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

Noncanonical base pairs play an important role in enabling the structural and functional complexity of RNA. Molecular recognition of such motifs is challenging because of their diversity, significant deviation from the Watson-Crick structures, and dynamic behavior, resulting in alternative conformations of similar stability. Triplex-forming peptide nucleic acids (PNAs) have emerged as excellent ligands for the recognition of Watson-Crick base-paired double helical RNA.

View Article and Find Full Text PDF

Deoxyribonucleic acid triplexes have potential roles in a range of biological processes involving gene and transcriptional regulation. A major challenge in exploiting the formation of these higher-order structures to target genes is their low stability, which is dependent on many factors including the length and composition of bases in the sequence. Here, different DNA base modifications have been explored, primarily using native mass spectrometry, in efforts to enable stronger binding between the triplex forming oligonucleotide (TFO) and duplex target sites.

View Article and Find Full Text PDF

In this study, a new triplex hairpin oligosensor was developed for the determination of a breast cancer biomarker using silicon quantum dots (Si QD) (λ = 370 nm, λ = 482 nm) as donor and gold nanoparticles (GNP) as an acceptor in a FRET (fluorescence resonance energy transfer) mechanism. In the triplex hairpin oligosensor, a triplex-forming oligonucleotide (TFO) labeled with Si QD and a single-strand DNA labeled with GNP form a hairpin shape with a triplex structure at the hairpin stem. In a turn-on mechanism, the triplex hairpin stem is opened in the presence of sequence-specific miRNA-155 which leads to the release of the Si QD-labeled TFO probe and recovery of the fluorescence signal.

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!