Mixed-backbone oligonucleotides as second generation antisense oligonucleotides: in vitro and in vivo studies
| Autor: | Zhiwei Jiang, Qiuyan Zhao, Lakshmi Channavajjala, Qiuyin Cai, Denise Shaw, Carl Saxinger, Ruiwen Zhang, Sudhir Agrawal, Allysen Roskey |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Male
Anti-HIV Agents Metabolic Clearance Rate Ribonuclease H Kidney Lymphocyte Activation Nucleic Acid Denaturation Virus Replication Hemolysis Cell Line Rats Sprague-Dawley Mice In vivo Oligoribonucleotides Animals Humans Lymphocytes RNase H Blood Coagulation Cells Cultured Multidisciplinary biology Base Sequence Oligonucleotide Triazines RNA Oligonucleotides Antisense Thionucleotides Biological Sciences In vitro Rats Kinetics Biochemistry Oligodeoxyribonucleotides Cell culture Drug Design biology.protein HIV-1 Spleen |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 94(6) |
| ISSN: | 0027-8424 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|