Gewirtz A M
University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Curr Opin Hematol. 1998 Jan;5(1):59-71. doi: 10.1097/00062752-199801000-00011.
The development of reliable gene disruption strategies, and their application in living cells, has proven to be an extraordinary important advance for cell and molecular biologists. Using the various available approaches, the specific functions of any given gene may now be investigated directly in the relevant cell type. Application of similar experimental tools in a clinical setting might prove to be equally valuable and could well form the basis of a monumental advance in the practice of clinical medicine. This seems particularly true at the present time because much progress has been made in understanding the molecular pathogenesis of many diseases, including cancer. For these reasons a tremendous amount of interest has been generated in the use of oligodeoxynucleotides to modify gene expression. However, in spite of some notable successes which are detailed in this review, oligonucleotides have generated controversy in regard to their mechanism of action, reliability, and ultimate therapeutic utility. Nevertheless, the potential power of the "antisense" approach remains undisputed, and its ultimate therapeutic utility is far reaching. Accordingly, the problems associated with the use of these compounds are clearly worth solving. It remains the hope of many laboratories that the day will soon come when these techniques will make an important contribution to the management of chronic myelogenous leukemia and other neoplastic disorders.
可靠的基因破坏策略的发展及其在活细胞中的应用，已被证明是细胞和分子生物学家取得的一项极其重要的进展。利用各种现有方法，现在可以直接在相关细胞类型中研究任何给定基因的特定功能。在临床环境中应用类似的实验工具可能同样有价值，并且很可能成为临床医学实践中一项重大进展的基础。目前尤其如此，因为在理解包括癌症在内的许多疾病的分子发病机制方面已经取得了很大进展。出于这些原因，人们对使用寡脱氧核苷酸来改变基因表达产生了极大的兴趣。然而，尽管本综述详细介绍了一些显著的成功案例，但寡核苷酸在其作用机制、可靠性和最终治疗效用方面仍存在争议。尽管如此，“反义”方法的潜在力量仍然无可争议，其最终治疗效用影响深远。因此，与使用这些化合物相关的问题显然值得解决。许多实验室仍然希望，这些技术对慢性粒细胞白血病和其他肿瘤性疾病的治疗做出重要贡献的那一天很快就会到来。
