Antisense oligonucleotides as therapeutic agents--is the bullet really magical?
Because of the specificity of Watson-Crick base pairing, attempts are now being made to use oligodeoxynucleotides (oligos) in the therapy of human disease. However, for a successful outcome, the oligo must meet at least six criteria: (i) the oligos can be synthesized easily and in bulk; (ii) the oligos must be stable in vivo; (iii) the oligos must be able to enter the target cell; (iv) the oligos must be retained by the target cell; (v) the oligos must be able to interact with their cellular targets; and (vi) the oligos should not interact in a non-sequence-specific manner with other macromolecules. Phosphorothioate oligos are examples of oligos that are being considered for clinical therapeutic trials and meet some, but not all, of these criteria. The potential use of phosphorothioate oligos as inhibitors of viral replication is highlighted.
Stein
C A
CA
Department of Medicine, Columbia University, New York, NY 10032.
Cheng
Y C
YC
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006564:Herpesviridae / Q000187:drug effects / Q000502:physiology; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D014176:Protein Biosynthesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D013873:Thionucleotides / Q000494:pharmacology / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D013873:Thionucleotides