Tuesday, June 08, 2010

DNA Robots to Hunt and Kill Cancer

DNA Robots to Hunt and Kill Cancer By: R. Colin Johnson
Assembling a molecular-sized robot using DNA was recently demonstrated by researchers aiming for nano-robots to detect disease markers on a cell, diagnose it and deliver a cargo of cancer-killing drugs as appropriate.

Deoxyribonucleic acid acid (DNA) holds the instructions that every living cell uses to grow, develop and fight disease. The material itself, however, can also be used as a building block for tiny machines with the ability to propel themselves—slashing aside tethers like a machete clears a path, then attaching a bond to move forward the way a winch pulls a truck.

Several years ago, Professor Milan Stojanovic at Columbia University demonstrated a DNA robot that resembled a spider in its ability to use its tentacles for self-propulsion. The spider was shown to be capable of "walking" through a "field" of DNA molecules, and cutting and bonding with them to propel itself. Unfortunately, the direction that the spider traveled was random, setting Stojanovic on a quest to find a way to direct its movement to a goal.

Stojanovic’s team reasoned that such a small robot could not be directed in the manner of a normal robot, which has a microprocessor programmed with navigational abilities. For tiny DNA robots, there is no internal mechanism to program. Instead, the researchers decided to program the environment with "bread crumbs," which could form a trail that the DNA robot could follow.

At such tiny scales, however, proteins like the DNA itself remained the best bet for creating such a trail. The team found the material it needed in the work of CalTech Professor Paul Rothemund, who had invented what he named DNA origami. Using what is called sequence-recognition in base pairs, DNA origami are "folded" from a long single strand of DNA, with several shorter helper strands that "staple" the long strand into the desired shape.

Artist’s rendering of a 4-nanometer-diameter robot (blue) cutting its feet (green) from protruding staples behind it as it walks forward by binding to staples ahead of it, leading down a path to its goal (red).

Stojanovic's team made its own DNA origami bread crumbs, each programmed with a specific instruction to any walker that happens by—like sign posts, except that they only measured 2 nanometers thick and 100 nanometers long. Together, the DNA origami bread crumbs were formed into a path that allowed Stojanovic's team to lead their DNA robots to a goal.

The 4-nanometer-diameter spiders were also constructed from protein, using four symmetrically placed "legs" that could selectively cut and bind to the DNA bread crumbs. By cutting off the protruding origami staples that tethered it, then binding to the next ones, the legs could propel the robot down the DNA path.

And by programming the shape of each DNA origami with specific intentions on which way the robot should go next, the researchers were able to direct the spider to follow prescribed routes. These autonomous molecular DNA robots were demonstrated to start, move, turn and stop while following a prescribed path. Applications include therapeutic medical devices that navigate by following natural DNA markers that identify cancer cells and enable the robot to deliver drugs only to those cells.

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