Autonomous nanomachines perform biologic functions in live cells in world’s first.


Nanomachines made from synthetic DNA motors have the potential to mimic natural protein motors in cells, however, the operation of synthetic DNA motors in living cells has not yet been demonstrated. The remarkable specificity and predictability of Watson–Crick base pairing make DNA an appealing construction material to build the synthetic motor systems.  Although various synthetic DNA motors have been tested in test tubes, the ultimate goal of introducing them into cells to perform biological functions has not yet been achieved.  Now, a study from researchers at University of Alberta develops working synthetic DNA motors in living cells. The team state that their study demonstrates how DNA motors can be used to accomplish specific biological functions in live cells.  The opensource study is published in the journal Nature Communications.

Previous studies show that to operate in living cells, synthetic DNA motors must confront the following challenges; first, all components of the motor system, including the motor and its track, must be readily taken up by living cells; second, the operation of the motor should be initiated by specific molecules within the cells; third, the motor has to be self-powered to enable autonomous intracellular walking, because external addition of fuel DNA strands or protein enzymes is not desirable; and finally, the operation of the motor in living cells should be monitored in real-time.  The current study develops a DNAzyme motor that operates in living cells in response to a specific intracellular target.

The current study develops a nanomachine from compartments made up of DNA enzyme molecules and substrates, consisting of the required fuels, DNA tracks, and a molecular switch.  The nanomachine is designed to detect a specific microRNA sequence found in breast cancer cells. Results show that when the DNA motor came into contact with the targeted molecules, it produced fluorescence as part of a reaction. The group were able to monitor the fluorescence, detecting which cells were cancerous and believe the findings show great promise for the early diagnosis of disease.

The researchers stress that the global medical community want the ability to detect cancer or disease markers in very minute amounts before the disease gets out of hand. They note that the trace amount of the target molecules that may be missed by other techniques can now be detected with their nanomachine.  They go on to add that in addition to the potential for improved disease diagnosis, DNA motors could also be used for precision drug delivery in patients. They explain that conventional targeted drug therapy delivers medicine to a selectively targeted site of action, yet it still affects molecules which are not diseased; with the DNA motor they hypothesize that a drug payload can be delivered and then released only when triggered by disease specific molecules.

The team surmise that their study demonstrates, for the first time, the operation of a synthetic DNA motor in living cells.  For the future, the researchers state that their aim is to expand the work to examine a wider range of disease markers. They conclude that further testing on the nanomachines is needed to better understand the full range of capabilities for drug delivery.

Source: University of Alberta

Cell-based Nano Machine Breaks Record. Vorticella cells with coils expanded. Credit: Image captured using the LCPolScope, developed by Shinya Inoue at the Marine Biological Laboratory, Woods Hole, MA; images by Danielle France.

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