When oligonucleotide probes are microinjected into cells to image the distribution of RNAs, they are rapidly sequestered into the nucleus. As a result, it is difficult to detect mRNAs in the cytoplasm of living cells. We were able to overcome this process by attaching tRNA transcripts to the probes. We show that when fluorescently labeled tRNAs, tRNAs with extensions at their 5' end, or chimeri...

630 Second-generation antisense oligonucleotides: structure-activity relationships and the design of improved signal-transduction inhibitors K.-H. Altmann*, D. Fabbrot, N. M. Dean$, T. Geigert, 6. P. Mania$, M. Mullert and P. Nickling *Ciba-Geigy Ltd., Central Research Laboratories, RI060 2.34, CH-4002 Basel, Switzerland, tCiba-Geigy Ltd , Pharmaceutical Division, Department of Oncology, CH-400...

Oligonucleotide microarrays are widely used in various biological studies. In this review, application of oligonucleotide microarrays for identifying binding sites and probing structure of RNAs is described. Deep sequencing allows fast determination of DNA and RNA sequence. High-throughput methods for determination of secondary structures of RNAs have also been developed. Those methods, however...

Transfection with antisense oligonucleotides was used to reduce calpain 1 activity to approximately 50% of normal values in cultured hippocampal slices. This had no detectable effects on baseline synaptic responses but greatly reduced the incidence and magnitude of long-term potentiation induced with a theta-burst stimulation paradigm. These results suggest that activation of calpain by repetit...

We have demonstrated recently that calreticulin, an intracellular calcium-binding protein, can interact with the alpha-subunits of integrin receptors via the highly conserved KXGFFKR amino acid sequence present in the cytoplasmic domains of all integrin alpha-subunits (Rojiani et al. (1991) Biochemistry 30, 9859-9866). Here we demonstrate that calreticulin can be co-localized by immunofluoresce...

Molecular imaging, the science that combines non-invasive in vivo imaging and molecular biology, has begun to use labelled oligonucleotides as radiotracers. Antisense oligonucleotides target gene expression at the RNA level, while aptamer oligonucleotides are designed to hit proteins of interest. Oligonucleotides for imaging cover a large range of applications, from the invention of new contras...

In an article published by Helvetica Chimica Acta in 1995, chemist P. Martin describes the synthesis of 2?-O-alkylated ribonucleosides for use therapeutic antisense oligonucleotides (ASOs). This work was motivated need a modified ribose structure that compatible with solid-phase protocols and that, when incorporated into oligonucleotide, would render it resistant to nucleases without attenuatin...

Integrins have become key targets for molecular imaging and for selective delivery of anti-cancer agents. Here we review recent work concerning the targeted delivery of antisense and siRNA oligonucleotides via integrins. A variety of approaches have been used to link oligonucleotides to ligands capable of binding integrins with high specificity and affinity. This includes direct chemical conjug...

Malignant pleural mesothelioma is a rare and aggressive tumor characterized by rapid progression, late metastases, and poor prognosis. In this study, we investigated the expression of survivin, a member of the inhibitors of apoptosis protein gene family, in mesothelioma and an antisense oligonucleotide-based gene therapy for mesothelioma using survivin as a target. Initially, we documented the ...

Early kidney differentiation is driven by local cell-cell interactions. The metanephrogenic mesenchyme stimulates the epithelial ureter bud to grow and branch, whereas the ureter bud stimulates the mesenchyme to convert into a new epithelium. These interactions may be dependent on local growth factors and their receptors. We studied the expression of receptors for nerve growth factors during ki...