Lung branching morphogenesis depends on mesenchymal-epithelial tissue interactions. Keratinocyte growth factor (KGF) has been implicated to be a regulator of these tissue interactions. In the present study, we investigated the role of KGF in early rat lung organogenesis. Reverse transcriptase-polymerase chain reaction analysis revealed KGF mRNA expression in the mesenchymal component of the 13-...

A novel 2',4'-BNA/LNA analog bridged by guanidine, termed as guanidine bridged nucleic acid (GuNA), was synthesized and incorporated into oligonucleotides. Thermal stabilities and nuclease resistance of GuNA-modified oligonucleotides were investigated and compared with those of 2',4'-BNA/LNA and natural DNA oligonucleotides. GuNA exhibited interestingly high binding affinity towards complementa...

Oligonucleotides containing internal triazole-3'-LNA linkages bind to complementary RNA with similar affinity and specificity to unmodified oligonucleotides, and significantly better than oligonucleotides containing triazole alone. In contrast LNA on the 5'-side of the triazole does not stabilise duplexes. Triazole-LNA confers great resistance towards enzymatic degradation relative to LNA alone.

We describe the preparation of several types of porous silicon (pSi) microparticles as supports for the solid-phase synthesis of oligonucleotides. The first of these supports facilitates oligonucleotide release from the nanostructured support during the oligonucleotide deprotection step, while the second type of support is able to withstand the cleavage and deprotection of the oligonucleotides ...

Codon randomization via degenerate oligonucleotides is a widely used approach for generating protein libraries. We use integer programming methodology to model and solve the problem of computing the minimal mixture of oligonucleotides required to induce an arbitrary target probability over the 20 standard amino acids. We consider both randomization via conventional degenerate oligonucleotides, ...

The covalent attachment of disulfide-modified oligonucleotides to a mercaptosilane-modified glass surface is described. This method provides an efficient and specific covalent attachment chemistry for immobilization of DNA probes onto a solid support. Glass slides were derivatized with 3-mercaptopropyl silane for attachment of 5-prime disulfide-modified oligonucleotides via disulfide bonds. An ...

Multidrug resistance-associated protein (MRP1) causes cellular drug resistance in several cancer cell lines. In this paper we show that antisense oligonucleotides decrease MRP1 expression in human leukaemia cells. We investigated biological activity of a series of 12 linear phosphorothioate oligonucleotides, complementary to several regions of MRP1 mRNA. The oligonucleotides were administered t...

DNA and RNA chromatography is extensively used for nucleic acid analysis. To better understand the chromatographic mechanisms by which DNA and RNA oligonucleotides are separated, ion pair reverse-pair ultra-high performance liquid chromatography (IP RP UHPLC) methods were developed. 11mer and 12mer DNA and RNA oligonucleotides of various compositions were used during this study. The first part ...

Antisense oligonucleotides are short strands of deoxyribonucleotides that are complementary to specifi c encoding mRNA sequences and can block gene expression. Their potential use as therapeutic and gene validation tools has elicited great interest. However, poor intracellular delivery into several tissues in living animals currently limits the range of in vivo applications of antisense oligonu...

We sought to use splice-switching antisense oligonucleotides to produce a model of accelerated ageing by enhancing expression of progerin, translated from a mis-spliced lamin A gene (LMNA) transcript in human myogenic cells. The progerin transcript (LMNA Δ150) lacks the last 150 bases of exon 11, and is translated into a truncated protein associated with the severe premature ageing disease, Hut...