Drug properties of second-generation antisense oligonucleotides: how do they measure up to their predecessors?
Antisense technology has progressed beyond the point of using only phosphorothioate oligodeoxynucleotides as therapeutic agents to looking at antisense molecules that contain additional chemical modifications as the next generation of therapeutic agents. These modifications are intended to improve the overall therapeutic properties by increasing potency, optimizing pharmacokinetic properties and improving the safety profile. This review will focus on the non-clinical pharmacokinetic and safety properties of 2'-O-methoxyethyl-modified oligonucleotides. Implications on the convenience and safe use of these compounds as therapeutic agents will be discussed.
Henry
S P
SP
Isis Pharmaceuticals Inc, Department of Toxicology and Pharmacokinetics, Carlsbad, CA 92007, USA. shenry@isisph.com
Geary
R S
RS
Yu
R
R
Levin
A A
AA
D000818:Animals; D000882:Haplorhini; D006801:Humans; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D054735:Phosphorothioate Oligonucleotides; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
C464616:ISIS104838; D016376:Oligonucleotides, Antisense; D054735:Phosphorothioate Oligonucleotides; D014409:Tumor Necrosis Factor-alpha