Harrington K J, Linardakis E, Vile R G
Molecular Medicine Program, Guggenheim 1836, Mayo Clinic, 200 1st Street SW, Rochester, MN 55902, USA.
Adv Drug Deliv Rev. 2000 Nov 15;44(2-3):167-84. doi: 10.1016/s0169-409x(00)00093-4.
The therapeutic index of cancer gene therapy approaches will, at least in part, be dictated by the spatial and temporal control of expression of the therapeutic transgenes. Strategies which allow precise control of gene transcription are likely to play a crucial role in the future pre-clinical and clinical development of gene therapy. In this review, we discuss these issues as they relate to tissue and tumor specific promoters. In addition, the exciting opportunities offered by the development of regulated gene expression systems using small molecules, radiation and heat are reviewed. It is realistic to expect that the future offers the prospect of amalgamating elements of a number of these different systems in a co-ordinated gene delivery approach with the potential to increase the efficacy and reduce the toxicity of treatment.
癌症基因治疗方法的治疗指数，至少部分地将由治疗性转基因表达的时空控制所决定。能够精确控制基因转录的策略可能在未来基因治疗的临床前和临床开发中发挥关键作用。在本综述中，我们将讨论与组织和肿瘤特异性启动子相关的这些问题。此外，还将综述利用小分子、辐射和热开发调控基因表达系统所带来的令人兴奋的机遇。可以预期，未来有可能将这些不同系统的要素以一种协调的基因递送方法进行整合，从而提高治疗效果并降低毒性。
