Branch A D
Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
Trends Biochem Sci. 1998 Feb;23(2):45-50. doi: 10.1016/s0968-0004(97)01155-9.
Antisense molecules and ribozymes capture the imagination with their promise of rational drug design and exquisite specificity. However, they are far more difficult to produce than was originally anticipated, and their ability to eliminate the function of a single gene has never been proven. Furthermore, a wide variety of unexpected non-antisense effects have come to light. Although some of these side effects will almost certainly have clinical value, they make it hard to produce drugs that act primarily through true antisense mechanisms and complicate the use of antisense compounds as research reagents. To minimize unwanted non-antisense effects, investigators are searching for antisense compounds and ribozymes whose target sites are particularly vulnerable to attack. This is a challenging quest.
反义分子和核酶因其在合理药物设计方面的前景和高度特异性而备受瞩目。然而，它们的生产难度比最初预期的要大得多，而且其消除单个基因功能的能力从未得到证实。此外，还发现了各种各样意想不到的非反义效应。尽管其中一些副作用几乎肯定具有临床价值，但它们使得难以生产主要通过真正反义机制起作用的药物，并使反义化合物作为研究试剂的使用变得复杂。为了尽量减少不必要的非反义效应，研究人员正在寻找其靶位点特别容易受到攻击的反义化合物和核酶。这是一项具有挑战性的任务。
