Mixed-backbone oligonucleotides as second generation antisense oligonucleotides: In vitro and in vivo studies

被引：230

作者：

Agrawal, S

Jiang, ZW

Zhao, QY

Shaw, D

Cai, QY

Roskey, A

Channavajjala, L

Saxinger, C

Zhang, RW

机构：

[1] UNIV ALABAMA,DEPT MED,DIV HEMATOL & ONCOL,BIRMINGHAM,AL 35294

[2] UNIV ALABAMA,DEPT PHARMACOL & TOXICOL,BIRMINGHAM,AL 35294

[3] UNIV ALABAMA,CTR COMPREHENS CANC,DIV CLIN PHARMACOL,BIRMINGHAM,AL 35294

[4] UNIV ALABAMA,CTR AIDS RES,BIRMINGHAM,AL 35294

[5] NCI,DIV BASIC SCI,BETHESDA,MD 20892

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1997年 / 94卷 / 06期

关键词：

pharmacokinetics; anti-HIV agents; coagulation; hemolytic complement;

D O I：

10.1073/pnas.94.6.2620

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Antisense oligonucleotides are being evaluated in clinical trials as novel therapeutic agents. To further improve the properties of antisense oligonucleotides, we have designed mixed-backbone oligonucleotides (MBOs) Bat contain phosphorothioate segments at the 3' and 5' ends and have a modified oligodeoxynucleotide or oligoribonucleotide segment located in the central portion of the oligonucleotide. Some of these MBOs indicate improved properties compared with phosphorothioate oligodeoxynucleotides with respect to affinity to RNA, RNase H activation, and anti-HIV activity. In addition, more acceptable pharmacological, in vivo degradation and pharmacokinetic profiles were obtained with these MBOs.

引用

页码：2620 / 2625

页数：6

共 23 条

[1] PHARMACOKINETICS, BIODISTRIBUTION, AND STABILITY OF OLIGODEOXYNUCLEOTIDE PHOSPHOROTHIOATES IN MICE [J].