title: Novel nanosensors for rapid analysis of telomerase activity.
abstract: Elevated telomerase levels are found in many malignancies, offering an attractive target for therapeutic intervention and diagnostic or prognostic purposes. Here we describe the use of a novel nanosensor developed for rapid screens of telomerase activity in biological samples. The technique utilizes magnetic nanoparticles that, on annealing with telomerase synthesized TTAGGG repeats, switch their magnet state, a phenomenon readily detectable by magnetic readers. We tested the efficacy of different telomerase inhibitors in crude human and murine samples and show that phosphorylation of telomerase regulates its activity. High-throughput adaptation of the technique by magnetic resonance imaging allowed processing of hundreds of samples within tens of minutes at ultrahigh sensitivities. Together, these studies establish and validate a novel and powerful tool for rapidly sensing telomerase activity and provide the rationale for developing analogous magnetic nanoparticles for in vivo sensing.
authors.affiliation: Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Grimm
authors.forename: J Manuel
authors.initials: JM
authors.lastname: Perez
authors.forename: Lee
authors.initials: L
authors.lastname: Josephson
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
mesh_terms: D015374:Biosensing Techniques; D002460:Cell Line; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D018625:Microscopy, Atomic Force / Q000379:methods; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism; D012680:Sensitivity and Specificity; D019098:Telomerase / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D009838:Oligodeoxyribonucleotides; D019098:Telomerase