Swarms of DNA nanorobots execute complex tasks in living animal

Swarms of DNA nanorobots execute complex tasks in living animal

Screenshot of DNA nanorobot designed using cadnano. Credit: Nature Nanotechnology.

Arguably the most exciting area of application for nanotechnology is medicine, especially sophisticated methods of drug delivery to increase potency and decrease adverse side effects. These span the range from current laboratory and clinical studies of incremental nanotechnology to visionary studies of complex nanomedical robots that will be feasible after the development of productive nanosystems and molecular manufacturing/high throughput atomically precise manufacturing. We frequently report here examples of promising applications of relatively simple nanoparticles, for example here, here, here, and here. However, as structural DNA nanotechnology rapidly expanded the repertoire of atomically precise nanostructures that can be fabricated, it became possible to fabricate functional DNA nanostructures incorporating logic gates to deliver and release molecular cargo for medical applications, as we reported a couple years ago (DNA nanotechnology-based nanorobot delivers cell suicide message to cancer cells). More recently, DNA nanorobots have been coated with lipid to survive immune attack inside the body. Now Christine Peterson forwards this news from Brian Wang at NextBIGfuture about another major advance in sophisticated DNA nanorobots for medical application “Ido Bachelet announces 2015 human trial of DNA nanobots to fight cancer and soon to repair spinal cords“:

At the British Friends of Bar-Ilan University’s event in Otto Uomo October 2014 Professor Ido Bachelet announced the beginning of the human treatment with nanomedicine. He indicates DNA nanobots can currently identify cells in humans with 12 different types of cancer tumors.

A human patient with late stage leukemia will be given DNA nanobot treatment. Without the DNA nanobot treatment the patient would be expected to die in the summer of 2015. Based upon animal trials they expect to remove the cancer within one month.

Within 1 or 2 years they hope to have spinal cord repair working in animals and then shortly thereafter in humans. This is working in tissue cultures.

Previously Ido Bachelet and Shawn Douglas have published work on DNA nanobots in the journal Nature and other respected science publications.]

[NOTE: This research was discussed in Nature but published in Science (abstract)] Back to Brian Wang:

One Trillion 50 nanometer nanobots in a syringe will be injected into people to perform cellular surgery.

The DNA nanobots have been tuned to not cause an immune response.

They have been adjusted for different kinds of medical procedures. Procedures can be quick or ones that last many days. …

This is the development of the vision of nanomedicine.
This is the realization of the power of DNA nanotechnology.
This is programmable DNA nanotechnology.

The DNA nanotechnology cannot perform atomically precise chemistry (yet), but having control of the DNA combined with advanced synthetic biology and control of proteins and nanoparticles is clearly developing into very interesting capabilities.

“This is the first time that biological therapy has been able to match how a computer processor works,” says co-author Ido Bachelet of the Institute of Nanotechnology and Advanced Materials at Bar Ilan University.

The team says it should be possible to scale up the computing power in the cockroach to that of an 8-bit computer, equivalent to a Commodore 64 or Atari 800 from the 1980s. Goni-Moreno agrees that this is feasible. “The mechanism seems easy to scale up so the complexity of the computations will soon become higher,” he says.

An obvious benefit of this technology would be cancer treatments, because these must be cell-specific and current treatments are not well-targeted. But a treatment like this in mammals must overcome the immune response triggered when a foreign object enters the body.

Bachelet is confident that the team can enhance the robots’ stability so that they can survive in mammals. “There is no reason why preliminary trials on humans can’t start within five years,” he says …

This optimism is baed on a publication last spring in Nature Nanotechnology “Universal computing by DNA origami robots in a living animal” [abstract, PDF on Bachelet’s web site]. The research is described at Phys.org “Researchers use DNA strands to create nanobot computer inside living animal“:

A team of researchers at Bar-Ilan University in Israel has successfully demonstrated an ability to use strands of DNA to create a nanobot computer inside of a living creature—a cockroach. In their paper published in Nature Nanotechnology, the researchers describe how they created several nanobot structures using strands of DNA, injected them into a living cockroach, then watched as they worked together as a computer to target one of the insects cells.

Prior research has shown that DNA strands can be programmable, mimicking circuits and even solving simple math problems. The team in Israel has now extended that work to show that such programmability can be used inside of a living organism to perform work, such as destroying cancer cells. …

Based on their 2012 Science paper above, they used scaffolded DNA origami nanorobots to implement a collision-based computer. Colliding with the proper protein cues, the nanorobot undergoes a drastic change in shape, exposing a payload molecule and making it available to engage target cells. The DNA architectures implement the logic gates AND, OR, XOR, NAND, NOT, CNOT and a half adder. The gate can also be opened by an external DNA key to activate the robot. This DNA key can now be mounted as a payload in one DNA nanorobot, thus assigning that robot a ‘positive regulator’ (P) phenotype. Robots of the opposite (N) phenotype can be loaded with a DNA clasp that cross links another robot’s gate, preventing it from opening or forcing it to close. Various architectures were designing by mixing P and N robots with effector (E) robots. These architectures were tested in adult cockroaches, which were selected because of very low nuclease activity, small systemic volume, and chemical compatibility with DNA structures. E robots were designed with an antibody to recognize the insect’s haemolmyph cells, analogous to human white blood cells. Flow cytometry to determine antibody binding to haemolymph cells was done after injecting various mixtures of nanorobots with or without two protein cues (the cellular growth factors PDGF and VEGF).

The architectures described in this paper are capable of processing at most two input bits. The authors point out, however, that errors in robot activation scale only linearly with the numbers of robot types present in the system. They show how a hypothetical system could be constructed using eight nanorobot types recognizing four protein cues to generate nine distinct nanorobots states to control three different therapeutic molecules. The authors point out that scaling their cockroach model to humans would require a four order of magnitude increase in robot quantity and using a nuclease-resistant analogue, like locked nucleic acid (LNA) instead of DNA. Echoing the enthusiasm of Brian Wang above, this work demonstrates that the sophistication of devices fabricated by using DNA or other nucleic acid nanotechnology is increasing rapidly. Perhaps the ultimate development of systems for position-controlled, atomically precise chemistry is not out of the question. And perhaps when we are reflecting on biomedical progress a decade or so hence, we will look back fondly on cyborg cockroaches.
—James Lewis, PhD

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