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 resi...
Here we tested the ability to augment the biological activity of the thrombin aptamer, d(GGTTGGTGTGGTTGG), by using locked nucleic acid (LNA) to influence its G-quadruplex structure. Compared to un-substituted control aptamer, LNA-containing aptamers...
Nucleic acids are able to adopt a plethora of structures, many of which are of interest in therapeutics, bio- or nanotechnology. However, structural and biochemical stability is a major concern which has been addressed by incorporating a range of mod...
LNA-i-miR-221 is a novel phosphorothioate backbone 13-mer locked nucleic acid oligonucleotide-targeting microRNA-221 designed for the treatment of human malignancies. To understand the pharmacokinetic properties of this new agent, including unbound/t...
The increase in antibacterial resistance is a serious challenge for both the health and defence sectors and there is a need for both novel antibacterial targets and antibacterial strategies. RNA degradation and ribonucleases, such as the essential en...
Our group previously developed a series of bridged nucleic acids (BNAs), including locked nucleic acids (LNAs), amido-bridged nucleic acids (AmNAs), and guanidine-bridged nucleic acids (GuNAs), to impart specific characteristics to oligonucleotides s...
Locked nucleic acid quantitative Real-Time PCR (LNA-qPCR) for IDH1/2 mutations in AML measurable residual disease (MRD) detection is rarely reported. LNA-qPCR was applied to quantify IDH1/2 mutants MRD kinetics in bone marrow from 88 IDH1/2-mutated A...
Oligonucleotides are key compounds widely used for research, diagnostics, and therapeutics. The rapid increase in oligonucleotide-based applications, together with the progress in nucleic acids research, has led to the design of nucleotide analogs th...
Duchenne muscular dystrophy (DMD) is a fatal disorder characterised by progressive muscle wasting. It is caused by mutations in the dystrophin gene, which disrupt the open reading frame leading to the loss of functional dystrophin protein in muscle f...
2′,4′-methylene bridged nucleic acid/locked nucleic acid (2′,4′-BNA/LNA; LNA) is a modified nucleic acid that improves the function of antisense oligonucleotide therapeutics. In particular, LNA in the DNA strand increases its...
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and multiple endocrine neoplasia-β (MENβ) are two long noncoding RNAs upregulated in multiple cancers, marking these RNAs as therapeutic targets. While traditional small-molecu...
The genome editing approach using the components of the CRISPR/Cas system has found wide application in molecular biology, fundamental medicine and genetic engineering. A promising method is to increase the efficacy and specificity of CRISPR/Cas-base...
Although circulating tumour DNA (ctDNA)-based next-generation sequencing (NGS) is a less invasive method for assessing ESR1 mutations that are essential mechanisms of endocrine therapy resistance in patients with oestrogen receptor-positive breast ca...
G-quadruplexes (G4s) are non-canonical nucleic acid secondary structures that have gathered significant interest in medicinal chemistry over the past two decades due to their unique structural features and potential roles in a variety of biological p...
Rifampicin-resistant tuberculosis (RR-TB) has become a major threat globally. This study aims to develop a new assay, RIF-RDp, to enhance the detection of RR-TB based on combined locked nucleic acid (LNA) probes with high-resolution melting curve ana...
Lung gene therapy for cystic fibrosis disease has not been successful due to several challenges such as the absence of an appropriate vector. Therefore, optimal delivery of emerging therapeutics to airway epithelial cells demands suitable non-viral s...
Bacterial resistance to antibiotics threatens the ability to treat life-threatening bloodstream infections. Oligonucleotides (ONs) composed of nucleic acid mimics (NAMs) able to inhibit essential genes can become an alternative to traditional antibio...
Salmonella enteritidis (SE) is an important factor causing foodborne disease, and electrochemical sensors have drawn much attention for SE prevention and detection due to their many advantages. A renewable electrochemical sensor using specially desig...
Previously, we have revealed that the miR-130 family (miR-130b, miR-301a, and miR-301b) functions as an oncomiR in bladder cancer. The pharmacological inhibition of the miR-130 family molecules by the seed-targeting strategy with an 8-mer tiny locked...
We demonstrate detection and quantification of bacterial load with a novel microfluidic one-pot wash-free fluorescence in situ hybridization (FISH) assay in droplets. The method offers minimal manual workload by only requiring mixing of the sample wi...
Locked nucleic acids (LNA) confer high thermal stability and nuclease resistance to oligonucleotides. The discovery of polymerases that accept LNA triphosphates has led us to propose a scheme for the amplification and re-generation of LNA-containing...
Ribosomal frameshifting (RFS) at the slippery site of SARS-CoV-2 RNA is essential for the biosynthesis of the viral replication machinery. It requires the formation of a pseudoknot (PK) structure near the slippery site and can be inhibited by PK-disr...
Transcription of the HIV-1 provirus generates a viral pre-mRNA, which is alternatively spliced into more than 50 HIV-1 mRNAs encoding all viral proteins. Regulation of viral alternative splice site usage includes the presence of splicing regulatory e...
The adult Göttingen Minipig is an acknowledged model for safety assessment of antisense oligonucleotide (ASO) drugs developed for adult indications. To assess whether the juvenile Göttingen Minipig is also a suitable nonclinical model for pediatric s...
Previously reported (S)-5′-C-aminopropyl-2′-arabinofluoro-thymidine (5ara-T) and newly synthesized (S)-5′-C-aminopropyl-2′-arabinofluoro-5-methyl-cytidine (5ara-MeC) analogs were incorporated into a series of antisense gapmers...
RNase H-dependent gapmer antisense oligonucleotides (ASOs) are a promising therapeutic approach via sequence-specific binding to and degrading target RNAs. However, the efficacy and mechanism of antiviral gapmer ASOs have remained unclear. Here, we i...
Spinal muscular atrophy (SMA) was added to the HHS Secretary’s Recommended Uniform Screening Panel for newborn screening (NBS) in 2018, enabling early diagnosis and treatment of impacted infants to prevent irreversible motor neuron damage. In a...
Thrombin binding aptamer (TBA) is one of the best-known G-quadruplex (G4)-forming aptamers that efficiently binds to thrombin, resulting in anticoagulant effects. TBA also possesses promising antiproliferative properties. As with most therapeutic oli...
Gapmer-type antisense oligonucleotides (ASOs) are an emerging class of therapeutic agents that directly inhibit pathogenic mRNA. In this study, three new 4′-C-substituted thymidine analogs were generated using a synthetic strategy recently esta...
Peptide-oligonucleotide conjugates (POCs) represent one of the increasingly successful albeit costly approaches to increasing the cellular uptake, tissue delivery, bioavailability, and, thus, overall efficiency of therapeutic nucleic acids, such as,...
Aptamers, and the selection process known as Systematic Evolution of Ligands by Exponential Enrichment (SELEX) used to generate them, were first described more than twenty years ago. Since then, there have been numerous modifications to the selection...
Blood feeding in Anopheles stephensi initiates a cascade of events that modulate several physiological functions in the mosquito. The midgut epithelium activates several of its molecules, most important among these being microRNAs, which regulate som...
Single nucleotide polymorphisms (SNPs) are single nucleotide variations which comprise the most wide spread source of genetic diversity in the genome. Currently, SNPs serve as markers for genetic predispositions, clinically evident disorders and dive...
Genome-edited (GE) crops are reaching consumers faster than the analytical infrastructure designed to monitor them. Unlike transgenic crops, most GE products carry only small sequence changes and no foreign DNA, making conventional element-based poly...
Background: Diabetic nephropathy is characterized by metabolic dysregulation, renal fibrosis, and impaired autophagy. MicroRNA-451 (miR-451) has been implicated in metabolic and stress-response pathways, but its role in diabetic kidney disease remain...
Here we investigated the refolding of Bacillus subtilis 6S-1 RNA and its release from σA-RNA polymerase (σA-RNAP) in vitro using truncated and mutated 6S-1 RNA variants. Truncated 6S-1 RNAs, only consisting of the central bubble (CB) flan...
Alcohol-associated liver disease (ALD) and metabolic dysfunction-associated steatotic liver disease (MASLD) arise from distinct etiological factors, but they share a broad spectrum of pathological features during disease progression, including steato...
Recently, KOD and its related DNA polymerases have been used for preparing various modified nucleic acids, including not only base-modified nucleic acids, but also sugar-modified ones, such as bridged/locked nucleic acid (BNA/LNA) which would be prom...
Fluorescence in situ hybridization (FISH) is a well-established technique that is used for a variety of purposes, ranging from pathogen detection in clinical diagnostics to the determination of chromosomal stability in stem cell research. The key ste...
This paper features the synthesis of thrombin-responsive, nucleic acid-gated, UiO-68 metal–organic framework nanoparticles (NMOFs) loaded with the drug Apixaban or rhodamine 6G as a drug model. Apixaban acts as an inhibitor of blood clots forma...
Oligonucleotide-based therapy has become an alternative to classical approaches in the search of novel therapeutics involving gene-related diseases. Several mechanisms have been described in which demonstrate the pivotal role of oligonucleotide for m...
Ticks serve as important vectors of a variety of pathogens. Recently, the viral and prokaryotic microbiomes in ticks have been explored using next-generation sequencing to understand the physiology of ticks and their interactions with pathogens. Howe...
Antisense technologies consist of the utilization of oligonucleotides or oligonucleotide analogs to interfere with undesirable biological processes, commonly through inhibition of expression of selected genes. This field holds a lot of promise for th...
Due to superior sensitivity compared to traditional microscopy, real-time PCR has been well established for the diagnosis of Giardia duodenalis in human stool samples. In this study, screening real-time PCRs for different target genes of G. duodenali...
DNA and RNA strand exchange is a process of fundamental importance in biology. Herein, we used a FRET-based assay to investigate, for the first time, the stand exchange kinetics of natural DNA, natural RNA, and locked nucleic acid (LNA)-modified DNA...
Antisense inhibition of gene expression is usually achieved using nuclease-resistant oligonucleotide analogs that promote mRNA degradation through RNase H or RNase P, or by steric hindrance of translation. Bridge nucleic acids (BNAs) are nucleotide a...
Lung cancer is the major cause of cancer-related deaths worldwide, thus developing effective methods for its early diagnosis is urgently needed. In recent years, microRNAs (miRNAs, miR) have been reported to play important roles in carcinogenesis and...
The RNA cleaving catalyst tris(2-aminobenzimidazole) when attached to the 5’ terminus of oligonucleotides cuts complementary RNA strands in a highly site-specific manner. Conjugation was previously achieved by the acylation of an amino linker b...
We investigate maneuvering superparamagnetic microparticles, or beads, in a remotely-controlled, automated way across arrays of few-micron-diameter permalloy disks. This technique is potentially useful for applying tunable forces to or for sorting bi...
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 photo...
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