Background: Spinal muscular atrophy (SMA) is a genetic motor neuron disease caused by mutations in the SMN1 (Survival Motor Neuron) gene, which leads to hypotonia, muscle weakness and respiratory involvement. Its most severe form, SMA type 1, starts before 6 months of life has high mortality due ventilatory failure. Nusinersen, first approved treatment for SMA, an antisense oligonucleotide intr...

Oligonucleotide probes are increasingly the method of choice for many modern DNA microarray applications. They provide higher target specificity, probe selection gives improved experimental control of hybridization properties, and targeting of specific gene subsequences allows better discrimination of highly similar targets such as splice variants or gene families. Only recently has there been ...

Oligodeoxynucleotides have been covalently linked to a 9-aminoacridine derivative via their 3'-phosphate group. Specific complexes are formed with the complementary sequence of the oligonucleotide. The stability is strongly increased due to intercalation of the acridine derivative. Absorption, fluorescence, nuclear magnetic resonance and circular dichroism have been used to characterize complex...

The codon-anticodon interaction on the ribosome occurs in the A site of the 30 S subunit. Aminoglycoside antibiotics, which bind to ribosomal RNA in the A site, cause misreading of the genetic code and inhibit translocation. Biochemical studies and nuclear magnetic resonance spectroscopy were used to characterize the interaction between the aminoglycoside antibiotic paromomycin and a small mode...

Approaches that improve upon the pharmacokinetic and pharmacodynamic properties of singlestrand antisense oligonucleotides are an active research topic. Antisense oligonucleotide phosphorothioates (ASOs) are highly protein bound. Therefore, it is likely that they traffic into and through cells via a protein to protein shuttling mechanism driven by binding affinity gradients.1 The ASO binding ev...

Multiple oligonucleotide (ON)-based therapeutic models have been developed to date including antisense oligonucleotides (ASOs), aptamer oligonucleotides (AOs) and short interfering RNA oligonucleotides (siRNA). In addition, modifications to oligonucleotide base-, backbone-, and ribosemoieties have all been introduced to limit nuclease-mediated degradation in therapeutic ONs. Mechanisms to resol...

Triple-helical DNA can be formed by oligonucleotides that bind as third strands of DNA in a sequencespecific manner in the major groove in homopurine/homopyrimidine stretches in duplex DNA. Such triple helix-forming oligonucleotides have been used to inhibit gene expression by blocking transcription factor access to promoter sites in transient expression assays. In an alternative approach to ge...

In this report, we present a characterization of the cell-specific expres slon of two human cytochrome P450 genes, CYPIAJ and CYP1BJ, by 2,3,7,S-tetrachlorodibenzo-p-dloxin (TCDD). The TCDD-dependent In ductionof CYPJAJhas beenstudiedextensivelyand servesas the proto type response for a TCDD-signaling pathway initiated by the reversible binding of TCDD to an Intracellular receptor [designated t...

De novo gene and genome synthesis enables the design of any sequence without the requirement of a pre-existing template as in traditional genetic engineering methods. The ability to mass produce synthetic genes holds great potential for biological research, but widespread availability of de novo DNA constructs is currently hampered by their high cost. In this work, we describe a microfluidic pl...

T4 polynucleotide kinase is widely used for 5'-phosphorylation of DNA and RNA oligonucleotide termini, but no natural protein enzyme is capable of 3'-phosphorylation. Here, we report the in vitro selection of deoxyribozymes (DNA enzymes) capable of DNA oligonucleotide 3'-phosphorylation, using a 5'-triphosphorylated RNA transcript (pppRNA) as the phosphoryl donor. The basis of selection was the...