Antisense oligonucleotides are synthetic genetic materials that interact with natural genetic material and modulate them in a systematic way. Antisense oligonucleotides as a form of molecular medicine to modulate gene function was first acknowledged in the late 1970s. This therapy involves blocking translation, thereby inhibiting protein formation. Recently, antisense technology has been resurr...

It is widely accepted that most cell types efficiently exclude oligonucleotides in vitro and require specific delivery systems, such as cationic lipids, to enhance uptake and subsequent antisense effects. Oligonucleotides are not readily transfected into leukaemia cell lines using cationic lipid systems and streptolysin O (SLO) is used to effect their delivery. We wished to investigate the opti...

Oligonucleotides containing Locked Nucleic Acids (LNA) to various extents and at various positions were evaluated for antisense activity, RNase H recruitment, nuclease stability and thermal affinity. In this work, two different diastereoisomers of LNA were studied: the beta-D-LNA and the alpha-L-LNA (abbreviated as beta-D-LNA and alpha-L-LNA). Our findings show that the best antisense activity ...

The use of antisense oligonucleotides as a therapeutic tool in modulating gene expression represents a newly established strategy for treating diseases. Such oligomers may be designed to complement a region of a specific gene or messenger RNA. Using this approach, oligonucleotides can serve as a potential block of transcription or translation through sequence-specific hybridization with targete...

Antisense technology provides outstanding promise for treatment of human disease, having broad applicability and high specificity. Although advances have been made in antisense oligonucleotide chemistry, leading to increased plasma and cellular stability, and decreased toxicity, considerable potential remains for the enhancement of oligonucleotide uptake for targeted delivery of oligonucleotide...

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...

BACKGROUND Kirsten ras (Ki-ras) mutations are common in gastrointestinal cancer and one codon 12 mutation, glycine to valine, is particularly aggressive in colorectal cancer. AIMS To investigate if this valine point mutation could be targeted with antisense oligonucleotides and to determine the efficacy of any antisense/mRNA interaction. METHODS Twenty nine antisense oligonucleotides were s...

Section Review: Biologicals & Immunologicals: Antisense oligonucleotides: Rational drug design for genetic pharmacology A. Kirk Field & John Goodchild To cite this article: A. Kirk Field & John Goodchild (1995) Section Review: Biologicals & Immunologicals: Antisense oligonucleotides: Rational drug design for genetic pharmacology, Expert Opinion on Investigational Drugs, 4:9, 799-821, DOI: 10.15...