Selection of RNA aptamers to the Alzheimer's disease amyloid peptide

被引:104
作者
Ylera, F
Lurz, R
Erdmann, VA
Fürste, JP
机构
[1] Harvard Univ, Sch Med, Inst Human Genet, Biotherapeut Dev Lab, Boston, MA 02115 USA
[2] Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA
[3] Max Planck Inst Mol Genet, D-14195 Berlin, Germany
[4] Free Univ Berlin, Inst Biochem, D-14195 Berlin, Germany
关键词
in vitro selection; SELEX; electron microscopy; gold labeling; high-affinity RNA; aptamer; amyloid; Alzheimer's disease;
D O I
10.1006/bbrc.2002.6354
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Alzheimer's disease is correlated with the deposition of amyloid peptides in the brain of the patients. The amyloid is thus a major target in the search for novel diagnostic and therapeutic approaches. The present work employs in vitro selection to develop new tools for the study of the Alzheimer's disease. The selection strategy enables the design of specific nucleic acids (aptamers) against virtually any target molecule. High-affinity RNA aptamers against the betaA4(1-40) were isolated from a combinatorial library of similar to10(15) different molecules. The apparent dissociation constants K-d of these aptamers are 29-48 nM. The binding of the RNA to the amyloid fibrils was confirmed by electron microscopy. The chemical synthesis of these nucleic acids enables tailor-made modifications. By introduction of specific reporter groups these RNAs can become suitable tools for analytical and diagnostic purposes. Thus, this study may introduce a new approach for diagnosis of the Alzheimer's disease. (C) 2002 Elsevier Science (USA).
引用
收藏
页码:1583 / 1588
页数:6
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