In vitro selection of RNA aptamers against a conserved region of the Plasmodium falciparum erythrocyte membrane protein 1

被引:46
作者
Barfod, Anders [2 ]
Persson, Tina [2 ]
Lindh, Johan [1 ]
机构
[1] Swedish Inst Infect Dis Control, Dept Parasitol Mycol & Water & Environm Microbiol, S-17182 Solna, Sweden
[2] Lund Univ, Dept Organ Chem, S-22100 Lund, Sweden
关键词
PFEMP1; SEQUESTRATION; IMMUNIZATION; ANTIBODIES; MALARIA; ANTIGEN; SURFACE; BIND;
D O I
10.1007/s00436-009-1583-x
中图分类号
R38 [医学寄生虫学]; Q [生物科学];
学科分类号
07 ; 0710 ; 09 ; 100103 ;
摘要
The var-gene encoding Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is known to play a major role in the pathogenicity of the P. falciparum parasite. The protein enables the parasite to adhere to the endothelial linings of small blood vessels (cytoadherence) as well as to non-infected erythrocytes (rosetting), thus preventing clearance from the bloodstream. The development and spread of resistance towards most anti-malarial drugs used for treatment and prevention of the most severe form of malaria truly emphasise the importance of a continuous research and development of new drugs. In this study we use Systematic Evolution of Ligands by EXponential enrichment (SELEX) methodology to isolate high-affinity ligands (aptamers). To validate the results from the SELEX in vitro selection, different aptamers have been selected against PfEMP1 in a live cell assay of P. falciparum strain FCR3S1.2, a highly rosetting strain. We have been able to show the rosette disrupting capacity of these SELEX-aptamers at concentrations of 33 nM and with 100% disruption at 387 nM. The described results show that RNA aptamers are promising candidates for adjunct therapy in severe malaria.
引用
收藏
页码:1557 / 1566
页数:10
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