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

Sudhir Agrawal | Zendy; Zhiwei Jiang | Zendy; Qiuyan Zhao | Zendy; Denise R. Shaw | Zendy; Qiuyin Cai | Zendy; Allysen Roskey | Zendy; Lakshmi S. Channavajjala | Zendy; Carl Saxinger | Zendy; Ruiwen Zhang | Zendy

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

Author(s) -

Sudhir Agrawal,

Zhiwei Jiang,

Qiuyan Zhao,

Denise R. Shaw,

Qiuyin Cai,

Allysen Roskey,

Lakshmi S. Channavajjala,

Carl Saxinger,

Ruiwen Zhang

Publication year - 1997

Publication title -

proceedings of the national academy of sciences

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.

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