Mixed-backbone oligonucleotides as second generation antisense oligonucleotides: In vitro and in vivo studies
AUTOR(ES)
Agrawal, Sudhir
FONTE
The National Academy of Sciences of the USA
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=20138Documentos Relacionados
- Antitumor activity and pharmacokinetics of a mixed-backbone antisense oligonucleotide targeted to the RIα subunit of protein kinase A after oral administration
- Mixed backbone antisense oligonucleotides: design, biochemical and biological properties of oligonucleotides containing 2'-5'-ribo- and 3'-5'-deoxyribonucleotide segments.
- Hybridization of 2′-ribose modified mixed-sequence oligonucleotides: thermodynamic and kinetic studies
- Morpholino antisense oligonucleotides: tools for investigating vertebrate development
- In vivo generation of highly abundant sequence-specific oligonucleotides for antisense and triplex gene regulation.