McKinney J, Guerrier-Takada C, Wesolowski D, Altman S
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA.
Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6605-10. doi: 10.1073/pnas.121180398. Epub 2001 May 29.
Narrow spectrum antimicrobial activity has been designed to reduce the expression of two essential genes, one coding for the protein subunit of RNase P (C5 protein) and one for gyrase (gyrase A). In both cases, external guide sequences (EGS) have been designed to complex with either mRNA. Using the EGS technology, the level of microbial viability is reduced to less than 10% of the wild-type strain. The EGSs are additive when used together and depend on the number of nucleotides paired when attacking gyrase A mRNA. In the case of gyrase A, three nucleotides unpaired out of a 15-mer EGS still favor complete inhibition by the EGS but five unpaired nucleotides do not.
窄谱抗菌活性的设计目的是降低两个必需基因的表达,一个编码核糖核酸酶P的蛋白质亚基(C5蛋白),另一个编码促旋酶(促旋酶A)。在这两种情况下,均设计了外部引导序列(EGS)使其与相应的mRNA形成复合物。使用EGS技术,微生物的活力水平降低至野生型菌株的10%以下。EGS共同使用时具有累加性,且在攻击促旋酶A mRNA时取决于配对的核苷酸数量。就促旋酶A而言,15聚体EGS中有三个未配对的核苷酸仍有利于EGS实现完全抑制,但五个未配对的核苷酸则不然。