Mixed-backbone oligonucleotides as second generation antisense oligonucleotides: In vitro and in vivo studies
Abstract
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) that 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.
Acknowledgments
We thank Y. Li, B. Chambless, Yufeng Li, and L. High for technical assistance. The safety studies of oligonucleotides were carried out at Frederick Research Center, Frederick, MD.
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Copyright © 1997, The National Academy of Sciences of the USA.
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Received: October 2, 1996
Accepted: December 30, 1996
Published online: March 18, 1997
Published in issue: March 18, 1997
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Acknowledgments
We thank Y. Li, B. Chambless, Yufeng Li, and L. High for technical assistance. The safety studies of oligonucleotides were carried out at Frederick Research Center, Frederick, MD.
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94 (6) 2620-2625,
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