Crooke S T
Isis Pharmaceuticals, Carlsbad, California 92008.
Curr Opin Biotechnol. 1992 Dec;3(6):656-61. doi: 10.1016/0958-1669(92)90012-8.
Rapid progress in oligonucleotide therapeutics has continued over the past year as major programs established in the past four years have grown and begun to be productive. Important advances were reported in the medicinal chemistry of oligonucleotides and in understanding their pharmacodynamic properties. Significant progress was made in understanding the pharmacokinetic and toxicologic properties of first generation analogs, particularly phosphorothioates and one oligonucleotide, ISIS 2105, entered clinical trials. Additionally, combinatorial approaches designed to identify oligonucleotides that may bind to a variety of targets were reported.
过去一年，寡核苷酸疗法持续取得快速进展，过去四年设立的主要项目不断发展并开始产生成果。寡核苷酸药物化学及其药效学性质的认识方面均有重要进展。在理解第一代类似物的药代动力学和毒理学性质方面取得了重大进展，特别是硫代磷酸酯类，一种寡核苷酸ISIS 2105进入了临床试验。此外，还报道了旨在鉴定可能与多种靶点结合的寡核苷酸的组合方法。
