Novel nanosensors for rapid analysis of telomerase activity.
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.
Grimm
Jan
J
Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Perez
J Manuel
JM
Josephson
Lee
L
Weissleder
Ralph
R
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
D009838:Oligodeoxyribonucleotides; D019098:Telomerase