Self-replicating Anti-viral Molecular Machines

Augmanity, a research company based in Rehovot, Israel, has synthesized molecular machines, made from nucleic acids, which are capable of digesting viral RNA and utilizing it to assemble additional copies of itself inside living cells.

The machine’s body plan combines several parts that build upon the target RNA, assembling an immobile, DNA:RNA 4-way junction, which contains a single gene encoding a hammerhead ribozyme (HHR). Full assembly of the machine’s body from its parts enables the subsequent elongation of the gene and transcription of HHR molecules, followed by HHR-mediated digestion of the target molecule. This digestion converts the target to a building block suitable for participation in the assembly of more copies of the machine, mimicking biological heterotrophy.

Above – Images of the prototype automaton attached to DNA rectangles.

The work was led by Ido Bachelet. In 2014, Ido had developed nanobots that could open and close based on molecular sensing. This was going to be the basis for nano-surgery. They had made billions of the devices and would inject them into patients. The company that made the nanobots was bought by Pfizer. There has been no reports on the progress toward nanosurgery from Pfizer. Now, Ido Bachelet appears to have left Pfizer and is working on more advanced nanorobots based upon DNA and RNA.

Augmanity researchers describe the general design of a prototypical machine, characterize its activity cycle and kinetics, and show that it can be efficiently and safely delivered into live cells. As a proof of principle, we constructed a machine that targets the Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) GP64 gene, and show that it effectively suppresses viral propagation in a cell population, exhibiting predator/prey-like dynamics with the infecting virus. In addition, the machine significantly reduced viral infection, stress signaling, and innate immune activation inside virus-infected animals. This preliminary design could control the behavior of antisense therapies for a range of applications, particularly against dynamic targets such as viruses and cancer.

The discovery and synthesis of the immobile DNA junction by Seeman, nearly 4 decades ago, emerged as a cornerstone of DNA nanotechnology, an expanding field with unique technological potential. The immobile junction enabled, for the first time, programming and control of the spatial positioning of matter at a single DNA base resolution, or approximately 3.5 angstroms.

In this work, a preliminary working prototype of such a system is reported. They describe a machine, or automaton, assembled from DNA and RNA, which incorporates structural and functional principles of DNA nanotechnology. The automaton is designed as an immobile, DNA:RNA 4-way junction assembled from 3 parts, and contains a single gene which encodes a hammerhead ribozyme (HHR). Full assembly of the automaton’s body from its parts enables the subsequent transcription of HHR molecules and HHR-mediated digestion of the target molecule. This digestion renders the target suitable for participation in the assembly of more copies of the automaton, essentially mimicking biological heterotrophy. The starting material for self-replication, and for the subsequent “lifecycle” of the automaton, is a small seed population of fully-assembled machines, and a non-limiting amount of the separate DNA parts required for the assembly of new copies of the machine.

The automaton they describe here was inspired by pathogenic viruses and viroids, and is designed to be delivered into and operate inside living, virus-infected cells. Inside the cells, the automaton’s goal is to counter viral infection by utilizing viral RNA as “food”.

The design reported here is modular, and can be adapted rapidly to counter new targets, for example viruses once their genome has been sequenced. In addition, it could lead to new types of biologically-inspired, programmable agents for a range of therapeutic applications. Interestingly, this machine highlights complex anatomy and a hypothetical, rudimentary mechanism for predation, plausible features of molecular life forms from the RNA world.

DNA origami folding. Previously-described DNA rectangles8 were re-designed using caDNAno33 to include 6 edge staples comprising the automaton S strand on its 3’ to enable rectangle-based assembly.

SOURCES – Biorxiv – An antiviral self-replicating molecular heterotroph
Written by Brian Wang,

12 thoughts on “Self-replicating Anti-viral Molecular Machines”

  1. I understand the reasoning: If it only replicates in the presence of the targeted virus, then there doesn't have to be enough of it present in the absence of the virus to screw things up. So, if everything works as intended, you get fewer side effects.

    I'd advise making it VERY heavily dependent on some "vitamin" that isn't found in nature, though. And have several means of causing it to self destruct.

  2. This sounds extremely irresponsible. It’s better to have it self assemble from parts made in a lab, but not self replicate.

    And if you really wanted to do replication, then you should design it to require a chemical not normally found in the body or in nature. You’d give the patient this extra chemical during treatment. And it would be unable to replicate without it.

    But even that can be risky. You want to make VERY sure that no mutation of your device will ever allow it to replicate without that vitamin.

    It’s safer to avoid self replication entirely.

  3. This is another one of those great tech possibilities that someone is turning into a possible nightmare because they want to add a little lets see if we can also.

    Self replicating anything most especially at the micro and below levels is a VERY BAD idea. Just because we can does not mean we should.

    A pint of these babies that could be IV into your blood stream to hunt down destroy X then go inert and pass out of your system would be a god send. The same that can replicate itself and then do who knows what is just a devils playground of bad ideas.

  4. Agreed. And having created it, Bachelet should take responsibility and immediately begin working on a way to safely destroy similar nanobots in case they escape into the wild – do it before that happens and they have a chance to mutate.

  5. At least it isnt making paperclips 🙂

    This sort of thing is the future, you should get use to the idea in general. As well as the idea that this sort of tech will soon be within technical reach of random idiots in their basements.

  6. Yeah – what could possibly go wrong?
    Feels unnecessary to do the replication inside cells. Just mass produce in factories and kill viruses please. Besides, big pharma will make much more money if people can't just copy their product with a blood sample.

  7. Any device that can self-replicate in the wild is a bad idea.

    And being able to do so inside our bodies is a degree below in the scale of worse-ness.

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