Sullenger B A
Department of Experimental Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Appl Biochem Biotechnol. 1995 Jul-Sep;54(1-3):57-61. doi: 10.1007/BF02787911.
The ability to target ribozymes to specifically cleave viral RNAs in vitro has led to much speculation about their potential therapeutic value as antiviral agents in vivo. To transfer a ribozyme's potential as an antiviral agent from test tubes to cells and organisms successfully, the characteristics that distinguish these settings must be considered. In vitro, ribozymes and substrate RNAs freely diffuse in solution in test tubes, and trans-cleavage reactions are dependent on a diffusive step. In eukaryotic cells, by contrast, many RNAs do not appear to diffuse freely. Instead, they appear to be highly compartmentalized and actively sorted to specific cellular locations. Such RNA trafficking may result in localization of substrate RNAs in a different compartment than ribozymes, which would effectively reduce substrate RNA availability to ribozymes and therefore limit the effectiveness of ribozymes as gene inhibitors.
在体外将核酶靶向特异性切割病毒RNA的能力引发了诸多关于其作为体内抗病毒剂潜在治疗价值的猜测。要成功地将核酶作为抗病毒剂的潜力从试管转移到细胞和生物体中，必须考虑区分这些环境的特征。在体外，核酶和底物RNA在试管溶液中自由扩散，反式切割反应依赖于扩散步骤。相比之下，在真核细胞中，许多RNA似乎不会自由扩散。相反，它们似乎高度分隔并被主动分选到特定的细胞位置。这种RNA运输可能导致底物RNA定位在与核酶不同的区室中，这将有效地降低底物RNA对核酶的可及性，从而限制核酶作为基因抑制剂的有效性。
