利用针对可变表面糖蛋白的血清稳定RNA适配体靶向非洲锥虫的可变表面。
Targeting the variable surface of African trypanosomes with variant surface glycoprotein-specific, serum-stable RNA aptamers.
作者信息
Lorger Mihaela, Engstler Markus, Homann Matthias, Göringer H Ulrich
机构信息
Department of Microbiology and Genetics, Darmstadt University of Technology, 64287 Darmstadt, Germany.
出版信息
Eukaryot Cell. 2003 Feb;2(1):84-94. doi: 10.1128/EC.2.1.84-94.2003.
African trypanosomes cause sleeping sickness in humans and Nagana in cattle. The parasites multiply in the blood and escape the immune response of the infected host by antigenic variation. Antigenic variation is characterized by a periodic change of the parasite protein surface, which consists of a variant glycoprotein known as variant surface glycoprotein (VSG). Using a SELEX (systematic evolution of ligands by exponential enrichment) approach, we report the selection of small, serum-stable RNAs, so-called aptamers, that bind to VSGs with subnanomolar affinity. The RNAs are able to recognize different VSG variants and bind to the surface of live trypanosomes. Aptamers tethered to an antigenic side group are capable of directing antibodies to the surface of the parasite in vitro. In this manner, the RNAs might provide a new strategy for a therapeutic intervention to fight sleeping sickness.
非洲锥虫可导致人类患昏睡病以及牛患那加那病。这些寄生虫在血液中繁殖，并通过抗原变异逃避受感染宿主的免疫反应。抗原变异的特征是寄生虫蛋白质表面的周期性变化，该表面由一种称为可变表面糖蛋白（VSG）的可变糖蛋白组成。我们采用SELEX（指数富集配体系统进化）方法，报告了对与VSG具有亚纳摩尔亲和力的血清稳定小RNA（即所谓的适体）的筛选。这些RNA能够识别不同的VSG变体，并与活锥虫的表面结合。连接到抗原侧基的适体能够在体外将抗体导向寄生虫表面。通过这种方式，这些RNA可能为对抗昏睡病的治疗干预提供一种新策略。
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