Open AccessMixed-backbone oligonucleotides as second generation antisense oligonucleotides: In vitro and in vivo studies
Author(s) -
Sudhir Agrawal,
Zhiwei Jiang,
Qian Zhao,
Denise R. Shaw,
Qiuyin Cai,
Allysen Roskey,
Lakshmi Channavajjala,
Carl Saxinger,
Ruiwen Zhang
Publication year - 1997
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.94.6.2620
Subject(s) - oligonucleotide , in vivo , rnase h , in vitro , rnase p , rna , biology , microbiology and biotechnology , biochemistry , chemistry , gene , genetics
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.