Selection of RNA aptamers to the Alzheimer's disease amyloid peptide.
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 approximately 10(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.
Ylera
Francisco
F
Biotherapeutics Development Laboratory, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA. ylera@hms.harvard.edu
Lurz
Rudi
R
Erdmann
Volker A
VA
Fürste
Jens Peter
JP
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000138:chemical synthesis / Q000302:isolation & purification* / Q000378:metabolism / Q000648:ultrastructure; D001483:Base Sequence; D001665:Binding Sites; D015723:Gene Library; D006801:Humans; D008024:Ligands; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000302:isolation & purification* / Q000378:metabolism; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000302:isolation & purification* / Q000378:metabolism / Q000648:ultrastructure; D012313:RNA / Q000138:chemical synthesis / Q000302:isolation & purification* / Q000378:metabolism / Q000648:ultrastructure
D016229:Amyloid beta-Peptides; D008024:Ligands; D009841:Oligonucleotides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D012313:RNA