Manual Antisense Research and Application (Handbook of Experimental Pharmacology)

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Publisher Summary During the past decade, intense efforts to develop and exploit antisense technology have been mounted. Recommended articles Citing articles 0.

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To better understand the metabolism of these agents, we studied the stability of several phosphorothioate oligodeoxynucleotides, their congeners, and second generation oligomer chemistries in rat liver homogenates. To examine metabolism, background nuclease activity was characterized in whole liver homogenates by using ISIS , a mer phosphodiester oligodeoxynucleotide. Nuclease activity could readily be detected in liver homogenates. Our data indicate that metabolism of phosphorothioate oligodeoxynucleotides was more complex than that of phosphodiesters for many reasons, including phosphorothioate oligodeoxynucleotide inhibition of nucleases and the presence of R p and S p stereoisomers.

Antisense Research and Application | Stanley T. Crooke | Springer

The rate of phosphorothioate metabolism also appeared to be influenced by sequence, with pyrimidine-rich compounds being metabolized to a greater extent than purine-rich oligomers. Other factors affecting stability included oligomer chemistry and length. Concomitant experiments performed in rats dosed systemically with the same compounds mimic the activities seen in vitro and suggest that this liver homogenate system is a valuable model with which to study the mechanism of metabolism of antisense oligonucleotides.

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Antisense Therapy: An Overview

We do not retain these email addresses. Skip to main content. Crooke , Mark J. Graham , Michael J. Martin , Kristina M.

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Lemonidis , Tad Wyrzykiewiecz and Lendell L. Journal of Pharmacology and Experimental Therapeutics January , 1 ;.

UCL MSc in Experimental Pharmacology and Therapeutics

Abstract Phosphorothioate antisense oligodeoxynucleotides are novel therapeutic agents designed to selectively and specifically inhibit production of various disease-related gene products.