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Antisense Oligonucleotides

Introduction

Antisense oligonucleotides refer to short, synthetic oligonucleotide that are complementary in sequence and upon specific hybridization to its cognate gene product induces inhibition of gene expression. Oligonucleotides, as short as 15 mer have the required specificity to inhibit gene expression of a particular gene by annealing to the cellular mRNA (1,2). The mechanism of gene expression is based on two properties; the first is the physical blocking of the translation process by the presence of the short double stranded region, secondly the presence of the RNA-DNA duplex is susceptible to cellular RNase H activity. RNase H cleaves the RNA-DNA duplex region of the mRNA thus preventing the faithful translation of the mRNA (3).

The stability of the RNA-DNA duplex in terms of hybridization and half-life is crucial to successful gene inhibition. Vigorous research activity in the area of nucleic acid chemistry has been devoted in developing novel base analogs that are resistant to degradation and that possess strong hybridization properties. This product profile aims at listing some analogs that meet the above criteria and are amenable to be synthesized by currently available standard DNA synthesis chemistry. This includes the classical phosphorothioate linkages (4), propyne analogs (5) and the latest locked nucleic acid (LNA) base analogs (6). We believe from cited reports that LNA substituted oligos with phosphorothioate linkages presents the most stable hybridization and are least susceptible to nuclease degradation (6).

At Gene Link in addition to the synthesis of these modified oligos, we routinely assist customers in the design of the oligos that are particularly suited to their application.

*License Agreement: Locked-nucleic Acid (LNA) phosphoramidites are protected by EP Pat No. 1013661, US Pat No. 6,268,490 and foreign applications and patents owned by Exiqon A/S. Products are made and sold under a license from Exiqon A/S. Products are for research purposes only. Products may not be used for diagnostic, clinical, commercial or other use, including use in humans. There is no implied license for commercial use, including contract research, with respect to the products and a license must be obtained directly from Exiqon A/S for such use.

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