The mdx mouse model of muscular dystrophy arose due to a nonsense mutation in exon 23 of the dystrophin gene. We have previously demonstrated that 2'-O-methyl phosphorothioate antisense oligonucleotides (AOs) can induce removal of exon 23 during processing of the primary transcript. This results in an in-frame mRNA transcript and subsequent expression of a slightly shorter dystrophin protein in...

CD23 gene is overexpressed and abnormally regulated in the most frequent adult leukemic disorder, B chronic lymphocytic leukemia (B-CLL). Switch on and off in the upregulation of surface CD23 expression consistently occurs in the early stage of normal B-cell activation, suggesting a key role for CD23 in this process. We show here that, after ligation of mlg in the presence of interleukin-4, the...

Numerous studies have revealed that Rap1 (Ras-proximate-1 or Ras-related protein 1), a small GTPase protein, plays a crucial role in mediating cAMP signaling in isolated cardiac tissues and cell lines. However, the involvement of Rap1 in the cardiac development in vivo is largely unknown. By injecting anti-sense morpholino oligonucleotides to knock down Rap1a and Rap1b in zebrafish embryos, and...

PURPOSE To explore the regulatory roles of antisense oligonucleotide (ASODN) of vascular endothelial growth factor receptor 2/ VEGFR2 (kinase insert domain-containing receptor, KDR) on the proliferation of PC-3 human prostate cancer cell line. METHODS Different concentrations of synthetic sense and antisense KDR oligonucleotides were transfected into PC-3 human prostate cancer cell line. The ...

Many eukaryotic and viral mRNAs, in which the first transcribed nucleotide is an adenosine, are decorated with a cap-1 structure, (7Me)G5'-ppp5'-A(2'OMe). The positive-sense RNA genomes of flaviviruses (Dengue, West Nile virus) for example show strict conservation of the adenosine. We set out to produce GpppA- and (7Me)GpppA-capped RNA oligonucleotides for non-radioactive mRNA cap methyltransfe...

The c-kit proto-oncogene encodes a receptor having tyrosine-specific kinase activity and has been mapped to chromosome 4 in the human and chromosome 5 in the mouse, at the dominant white spotting locus (W). Mutations at the W locus affect various aspects of murine hematopoiesis. The c-kit proto-oncogene has been shown to be expressed by leukemic myeloblasts, but not by normal unseparated human ...

RNA oligonucleotides have emerged as a new class of biologicals that can silence gene expression but also stimulate immune responses through specific pattern-recognition receptors. The development of effective delivery systems remains a major challenge for the therapeutic application of the RNA oligonucleotides. In this study, we have established a novel biodegradable carrier system that is hig...

Monocytes are important target cells for anti-inflammatory antisense strategies. However, monocytes are characterized by strong phagocytic and catalytic activity which may limit the effect of antisense oligonucleotides. Intracellular distribution of oligonucleotides in monocytes and the effect of cationic lipids on oligonucleotide uptake in monocytes and other leukocytes have not been evaluated...

In order to facilitate the use of biomolecular markers in clinical medicine, devices are urgently needed that are highly sensitive, specific, cost effective, and automated. Great strides have been made in this area with elegant sensing systems employing nanomaterials, microfluidics, and increasingly sophisticated device design. The direct analysis of most types of clinical samples requires femt...