Nano-robots and the Manipulation of Cellular Systems

Developments in biotechnology has allowed the mind of a single scientist to create complex structures using DNA strands. Using the flexibility and durability of DNA, Paul Rothemund of CalTech, used short oligonucleotide “staple” strands to fix a long piece of DNA to the desired shape. Though the complexity of his designs were impressive, they were first dismissed because people believed his idea, the DNA origami, had no real use. In time, Rothemund’s idea became the inspiration for the design of nanorobots capable of performing specific functions in the molecular scale.

In A Logic-Gated Nanorobot for Targeted Transport of Molecular Payloads by Douglas, Bachelet and Church, the DNA origami technique was employed to design a DNA device that can uptake and release a desired molecule by the clasping and unclasping of its opening. The design’s intention is to transport cellular signaling molecules towards a site of interest in order to induce desired cellular functions. The nanorobot’s robustness and abilities are tested through series of experiments in the test. Showing a significant result, the relative success of the design is a small step forward in biotechnology where the dream of specific targeting therapy and other cellular level activities may yet be achieved.

The device’s design is both intricate yet simple. Though its components are complex since it is composed of DNA and complementary “staples” that are highly specific for shape retention, the nanorobot can be best understood observing it as a whole. The device is roughly made up of two large domains. The most important design aspect of the device is that the molecules being delivered are securely sealed within the nanorobot. Utilizing a clasp system designed with aptamer locks that only open in certain combination of antigen keys, the two domains that make up the nanorobot are held shut with themolecules bound within. Only when the locks recognize the specific keys does the nanorobot reconfigure, causing the two halves to open and expose its contents. The goal of the nanorobot’s function is strategic targeting ability. Whether the molecule is a drug that could cause harm to healthy tissues or signaling molecules that need to be bound to specific cell types, the nanorobot should be able to deliver its payload without interference till it reaches its destination. This lock and key design allows for a controlled delivery, the key to the nanorobot’s purpose.

To test the performance of the logic-gating mechanism, three different versions of the nano-robot were used to see which would selectively bind to a single cell type most effectively. The tree versions of the nano-robots are a permanently closed version in which guide staples were not removed, an open version in which no guide staples or locks were included, and a gated version using two locks. Out of the three, the gated version discriminated between the two cell types, only binding to NKL cells. To further simulate physiological conditions, healthy cells were added. In response, the gated version was able to discriminate the different cells with high precision.

The ability of an activated robot was then tested to see if nano-robots were able to interface with cells and stimulate their signaling in separate inhibition and activation tasks. When leukemia cells were targeted with the gated-version of nano-robots loaded with a combination of antibodies, growth arrest was induced.

DNA is a natural biocompatible and biodegradable material, which is why DNA nanotechnology is recognized to hold the potential of becoming a novel delivery mechanism for drugs and molecular signals. However, there have been significant challenges to the practice usage of DNA nanotechnology. These challenges include the various microenvironment in the human body and multiple cells containing identical antigen keys that have the potential to unlock the nanorobots in an undesired manner. But with the understanding and success the nanorobots show in specific tests, there still lies a chance that nanorobots will become the breakthrough method of clinical treatment.

Douglas S, Bachelet I, Church G. A Logic-Gated Nanorobot for Targeted Transport of Molecular Payloads. Science335, 831-834. (2014)

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