A Telomerase-Assisted Strategy for Regeneration of DNA Nanomachines in Living Cells

DNA nanomachines have been engineered into diverse personalized devices for diagnostic imaging of biomarkers; however, the regeneration of DNA nanomachines in living cells remains challenging. Here, we report an ingenious DNA nanomachine that can implement telomerase (TE)-activated regeneration in living cells. Upon apurinic/apyrimidinic endonuclease 1 (APE1)-responsive initiation of the nanomachine, the walker of the nanomachine moves along tracks regenerated by TE, generating multiply amplified signals through which APE1 can be imaged in situ. Additionally, augmentation of the signal due to the regeneration of the nanomachines could reveal differential expression of TE in different cell lines. To the best of our knowledge, this is the first proof-of-concept demonstration of the use of biomarkers to assist in the regeneration of nanomachines in living cells. This study offers a new paradigm for the development of more applicable and efficient DNA nanomachines.

Automated summary

Researchers have developed a clever DNA nanomachine that can regenerate in living cells through the activation of telomerase (TE). The nanomachine moves along tracks regenerated by TE and generates amplified signals, allowing for the imaging of apurinic/apyrimidinic endonuclease 1 (APE1) in situ. The regeneration of the nanomachines also reveals differential expression of TE in different cell lines. This study demonstrates the potential of using biomarkers to assist in the regeneration of nanomachines in living cells and opens up new possibilities for the development of more applicable and efficient DNA nanomachines.