Stein C A
Department of Medicine, Columbia University Comprehensive Cancer Center, New York, NY 10032.
Leukemia. 1992 Oct;6(10):967-74.
The high specificity of binding of oligodeoxynucleotides to their target mRNA has resulted in suggestions that these compounds may be useful as therapeutic agents against human cancer. While many successful anti-sense experiments have been reported in the literature, significant obstacles to widespread therapeutic use remain. These include nuclease sensitivity, non-sequence specificity, and uncertainties regarding optimum choice of mRNA target. Other significant problems include lack of information concerning cellular pharmacology and pharmacokinetics, and relatively little data concerning optimum dosing schedules. This review attempts to provide current information about these issues, which have such a strong impact on this exciting and rapidly growing field.
寡脱氧核苷酸与其靶mRNA结合的高特异性使得人们认为这些化合物可能作为抗人类癌症的治疗剂有用。虽然文献中已报道了许多成功的反义实验，但广泛治疗应用仍存在重大障碍。这些障碍包括核酸酶敏感性、非序列特异性以及mRNA靶点最佳选择的不确定性。其他重大问题包括缺乏关于细胞药理学和药代动力学的信息，以及关于最佳给药方案的数据相对较少。本综述试图提供有关这些问题的当前信息，这些问题对这个令人兴奋且迅速发展的领域有如此强烈的影响。
