Perspectives in antisense therapeutics

被引：68

作者：

Agrawal, S ^{[1
]}

Iyer, RP ^{[1
]}

机构：

[1] Hybridon Inc, Cambridge, MA 02139 USA

来源：

PHARMACOLOGY & THERAPEUTICS | 1997年 / 76卷 / 1-3期

关键词：

oligonucleoside phosphorothioates; mixed-backbone oligonucleotides; pharmacokinetics; oral bioavailability; toxicology;

D O I：

10.1016/S0163-7258(97)00108-3

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Modulation of gene expression using oligonucleotides (oligos) is currently an area of intense activity, both from therapeutic, as well as research perspectives. To develop oligos as therapeutic agents, in addition to demonstrable biological activity, in vico metabolic stability, tissue disposition and pharmacokinetics are important considerations. Oligodeoxynucleoside phosphorothioates are the first-generation antisense analogs that have been studied extensively, and are in clinical trials against a number of disease indications. In an effort to improve the antisense properties of these compounds, mixed-backbone oligos incorporating different chemical modifications have been synthesized and evaluated for antisense activity, The present review will provide an overview of the pharmacokinetics and toxicology following intravenous, intraperitoneal, subcutaneous and oral administration of mixed-backbone oligos as second-generation antisense therapeutics. (C) 1997 Elsevier Science Inc.

引用

页码：151 / 160

页数：10

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