Gibson I
School of Biological Sciences, University of East Anglia, Norwich, UK.
Cancer Metastasis Rev. 1996 Sep;15(3):287-99. doi: 10.1007/BF00046343.
This review has looked at the wide-ranging research initiatives in the field of antisense technology. It starts with the philosophy behind antisense DNA and the production of antisense RNA from genetic constructs and raises the various problems which are being addressed. These include uptake into cells, targeting the substrate sequence and cells, the stability of the antisense molecules and pharmokinetic considerations within animals. The review talks of the positive results attained in vitro and in vivo in animal and plant experiments but also addresses the problems many workers have faced in the field. It attempts to resolve these differences in terms of the need for further understanding of the mechanisms by which the positive results have been obtained. The novel use of catalytic ribozymes (RNA) in downregulating genes is also discussed in similar terms to antisense DNA and RNA. By taking a case study with a human leukaemia the review delves into the mysteries of how different results can be resolved by improving the design of ribozymes thereby increasing specificity and preventing aberrant reactions. It is concluded that despite a lack of understanding of how the biological effects have come about in vitro and in vivo the clinical and research developments should resolve the issue of antisense potential for rational drug development.
本综述探讨了反义技术领域广泛的研究计划。它从反义DNA背后的原理以及从基因构建体产生反义RNA开始，并提出了正在解决的各种问题。这些问题包括进入细胞、靶向底物序列和细胞、反义分子的稳定性以及动物体内的药代动力学考虑因素。综述谈到了在动物和植物实验中体外和体内取得的积极成果，但也涉及了许多研究人员在该领域面临的问题。它试图根据需要进一步了解获得积极成果的机制来解决这些差异。催化核酶（RNA）在下调基因方面的新用途也与反义DNA和RNA以类似的方式进行了讨论。通过以人类白血病为例，综述深入探讨了如何通过改进核酶设计来解决不同结果的谜团，从而提高特异性并防止异常反应。结论是，尽管对体外和体内生物学效应如何产生缺乏了解，但临床和研究进展应能解决反义技术在合理药物开发方面的潜力问题。
