Evaluation of intracellular telomerase activity through cascade DNA logic gates

Abstract

Telomerase plays a vital role in cancer and aging, and telomerase activity detection has drawn great attention recently. However, a feasible in situ imaging system for intracellular telomerase is still a challenge. Here, we develop a novel approach to image intracellular telomerase activity using DNA-based computation. A cascade nucleic acid logic gate that responded to intracellular telomerase was constructed. A telomerase substrate (TS) probe, extended by intracellular telomerase, worked as an input to initiate computation cascades. In this way, intracellular telomerase could be clearly indicated by fluorophore labeled nucleic acids as the output. Through one-step incubation, evaluation of the intracellular telomerase activity for a HeLa cell line and the ability to differentiate cancer cells from normal cells could be realized. Furthermore, the response of intracellular telomerase activity to a telomerase-inhibiting model drug was observed using the proposed method. Thus, this intracellular telomerase computation device will allow improvements in studying the relationship between telomerase and cancer, and may help to develop telomerase inhibitors. This finding also expands the applications of DNA computational techniques in cells.